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FTR #1131 This program was recorded in one, 60-minute segment.
Introduction: This program continues discussion of Moderna from FTR #1130. The firm’s mRNA (messenger RNA) vaccine that was highlighted in that program is a major topic of discussion in this one as well.
Do note that DARPA support for Moderna and their work on “gene driving” technology in the context of that vaccine.
Introducing the topic of Moderna’s SARS Cov‑2 vaccine as a money maker for both Moderna and as a driver for the market as a whole, we note last Monday’s announcement which generated a major boost in the value of Moderna’s stock and a strong, general rally. The latter apparently stems from optimism that a successful vaccine will alleviate the economic damage from Covid-19.
A MarketWatch piece about the rapid fluctuation of Moderna’s stock underscores the significance of the timing of an announcement casting Moderna’s vaccine trial in overly optimistic light:
- Moderna’s CEO (Stephen Bancel) and CFO (Lorence Kim) both sold stock on Friday, in accordance with prearranged transactions. Bear in mind, that (as discussed in FTR #1130), Moderna’s stock was trading at $23.46 at the beginning of the year, and the company–which has never marketed a vaccine–was the beneficiary of $483 million dollars in federal funding earlier in the year.) ” . . . . On Friday, Bancel sold 11,046 shares at a weighted average price of $65.56 for about $724,200, as part of a predetermined trading plan adopted Dec. 28, 2018, according to a Form 4 filing with the Securities and Exchange Commission. He also disposed of 1,577 shares as part of a ‘bona fide’ gift. . . . Also, on Friday, Kim sold 20,000 shares at a weighted average price of $65.53 for about $1.31 million, as part of a predetermined trading plan. . . .”
- Kim also simultaneously bought and sold shares of his firm for a net profit of $16.79 million on Monday, the day of an overly optimistic announcement by Moderna. The fortuitously timed Moderna announcement made the firm’s CFO roughly $4 million: ” . . . . On Monday, he [Kim] exercised options to buy 241,000 shares at a weighted average price of $12.45 for about $3 million, also as part of a predetermined plan. At the same time, Kim executed sales of 241,000 shares, at a weighted average price of $82.12 for about $19.79 million. That means Kim netted about $16.79 million on the simultaneous buy and sale of shares. . . . with Monday’s stock price surge following the announcement of early data on its vaccine candidate potentially adding $4 million to Kim’s coffers. . . .”
- The above-referenced announcement by Moderna led to a dramatic increase in Moderna’s stock and boosted the market as a whole. Moderna announced that evening that it would sell $1.34 billion in stock to help its vaccine operation: ” . . . . Shares of Moderna closed at a record high of $80.00 on Monday after the company released a slice of positive interim clinical data from the first phase of its COVID-19 vaccine trial. That night it announced it would sell $1.34 billion in stock to help fund manufacturing costs associated with the experimental COVID-19 vaccine. . . .”
- Moderna’s stock nosedived at the end of the trading day on Tuesday, due to a critical article from Stat News: ” . . . . The stock took a nose dive on Tuesday, closing at $71.67, likely due in some degree to a Stat News story that questioned a lack of clinical clarity in the data it provided to investors. . . .”
- Moderna’s announcement was critically assessed by Stat News, which pointed out that the results were incomplete at best: ” . . . . In a clinical-trial data disclosure on Monday, Moderna shared that eight out of 45 participants in its COVID-19 vaccine study developed neutralizing antibodies, a decision that Stat’s Helen Branswell described as a ‘reason for caution.’ It didn’t share information about the immune response to the experimental vaccine in the remaining 37 participants. . . .”
- Nonetheless, Moderna’s stock–bolstered by government investment–has been on a dramatic upward swing: ” . . . . The company’s stock was up 3.8% in trading on Wednesday. Year-to-date, it has soared 270.2%, even though the company has no approved products. . . .”
There are serious questions about the substance of Moderna’s statement:
- Moderna’s much touted report on its vaccine—which triggered an upsurge in the markets on Monday—appears to have been incomplete, at best, and purposefully deceptive, at worst. “ . . . . While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data.. . . . If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words. Even the figures the company did release don’t mean much on their own, because critical information — effectively the key to interpreting them — was withheld. . . .”
- Part of the reason for alarm and skepticism concerns the behavior of the NIAID—whose director is Anthony Fauci: “ . . . . The National Institute for Allergy and Infectious Diseases has partnered with Moderna on this vaccine. Scientists at NIAID made the vaccine’s construct, or prototype, and the agency is running the Phase 1 trial. This week’s Moderna readout came from the earliest of data from the NIAID-led Phase 1. NIAID doesn’t hide its light under a bushel. The institute generally trumpets its findings, often offering director Anthony Fauci . . . or other senior personnel for interviews. But NIAID did not put out a press release Monday and declined to provide comment on Moderna’s announcement. . . .”
- To begin with, Moderna’s announcement was only statistically substantive for 8 of the 45 volunteer subjects: “ . . . . The company’s statement led with the fact that all 45 subjects (in this analysis) who received doses of 25 micrograms (two doses each), 100 micrograms (two doses each), or a 250 micrograms (one dose) developed binding antibodies. Later, the statement indicated that eight volunteers — four each from the 25-microgram and 100-microgram arms — developed neutralizing antibodies. Of the two types, these are the ones you’d really want to see. We don’t know results from the other 37 trial participants. . . .”
- It is possible that neutralizing antibodies may have been developed in the 37 test subjects whose data was not released because the testing process is exacting. Still the statement warrants caution, at the least. “ . . . . This doesn’t mean that they didn’t develop neutralizing antibodies.Testing for neutralizing antibodies is more time-consuming than other antibody tests and must be done in a biosecurity level 3 laboratory. Moderna disclosed the findings from eight subjects because that’s all it had at that point. Still, it’s a reason for caution . . . .”
- In addition, the age of the subjects was not released and that is relevant. “ . . . . Separately, while the Phase 1 trial included healthy volunteers ages 18 to 55 years, the exact ages of these eight people are unknown. If, by chance, they mostly clustered around the younger end of the age spectrum, you might expect a better response to the vaccine than if they were mostly from the senior end of it. And given who is at highest risk from the SARS-CoV‑2 coronavirus, protecting older adults is what Covid-19 vaccines need to do. . . .”
- In addition, there was no data released as to the durability of the neutralizing antibodies. If, for the sake of argument, they are not long-lasting, the utility of the vaccine is negligible. “ . . . . The report of neutralizing antibodies in subjects who were vaccinated comes from blood drawn two weeks after they received their second dose of vaccine. Two weeks. ‘That’s very early. We don’t know if those antibodies are durable,’ said Anna Durbin, a vaccine researcher at Johns Hopkins University. . . .”
- Still another point of contention/alarm concerns the variability in neutralizing antibodies among recovered patients: “ . . . . But studies have shown antibody levels among people who have recovered from the illness vary enormously; the range that may be influenced by the severity of a person’s disease. John ‘Jack’ Rose, a vaccine researcher from Yale University, pointed STAT to a study from China that showed that, among 175 recovered Covid-19 patients studied, 10 had no detectable neutralizing antibodies. Recovered patients at the other end of the spectrum had really high antibody levels. So though the company said the antibody levels induced by vaccine were as good as those generated by infection, there’s no real way to know what that comparison means. . . .”
- It is less than encouraging that Moderna disclosed that more relevant data will be disclosed in a report to be released in conjunction with NIAID: “ . . . . STAT asked Moderna for information on the antibody levels it used as a comparator. The response: That will be disclosed in an eventual journal article from NIAID, which is part of the National Institutes of Health. . . .”
- Ann Durbin was struck by the wording of Moderna’s release: “ . . . . Durbin was struck by the wording of the company’s statement, pointing to this sentence: ‘The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.’ ‘I thought: Generally? What does that mean?’ Durbin said. Her question, for the time being, can’t be answered. . . .”
- Jack Rose commented on the opaque nature of Moderna’s release: “. . . . Rose said the company should disclose the information. ‘When a company like Moderna with such incredibly vast resources says they have generated SARS‑2 neutralizing antibodies in a human trial, I would really like to see numbers from whatever assay they are using,’ he said. . . .”
- To date, Moderna issues press releases, not papers that can be vetted by the scientific community: “ . . . . It doesn’t publish on its work in scientific journals. What is known has been disclosed through press releases. That’s not enough to generate confidence within the scientific community. ‘My guess is that their numbers are marginal or they would say more,’ Rose said about the company’s SARS‑2 vaccine, echoing a suspicion that others have about some of the company’s other work. ‘I do think it’s a bit of a concern that they haven’t published the results of any of their ongoing trials that they mention in their press release. They have not published any of that,’ Durbin noted. . . .”
After summarizing a highly technical article warning that of the possible consequences of introducing a SARS Cov‑2 vaccine that generates inadequately high levels of antibodies, we detail a 2016 STAT News article about Moderna highlights a number of areas of concern, given the speed and relatively opaque nature of the potential introduction of its Covid-19 vaccine.
The financing of the company by DARPA, and Moncef Slaoui’s joining with Four Star General Perna (elevated by the Chairman of the Joint Chiefs of Staff, General Mark A. Milley) are of additional concern.
- As of 2016, Moderna had the largest valuation of any private biotech firm and former employees felt that Moderna prized money over science. Note that, as will be reviewed later in the program, its stock has risen exponentially as a result of the injection of hundreds of millions of dollars. Bear in mind that Moderna has also been underwritten by DARPA. “ . . . . Moderna is worth more than any other private biotech in the US, and former employees said they felt that Bancel prized the company’s ever-increasing valuation, now approaching $5 billion, over its science. . . .”
- Moderna has maintained a culture of secrecy, which in 2016, applied to the first two products undergoing phase 1 trials: “ . . . . Moderna just moved its first two potential treatments — both vaccines — into human trials. In keeping with the culture of secrecy, though, executives won’t say which diseases the vaccines target, and they have not listed the studies on the public federal registry, ClinicalTrials.gov. Listing is optional for Phase 1 trials, which are meant to determine if a drug is safe, but most companies voluntarily disclose their work. . . .”
- Protein therapy has been a driving economic and therapeutic factor in the pharmaceutical business: “ . . . . For decades, companies have endeavored to craft better and better protein therapies, leading to new treatments for cancer, autoimmune disorders, and rare diseases. Such therapies are costly to produce and have many limitations, but they’ve given rise to a multibillion-dollar industry. The anti-inflammatory Humira, the world’s top drug at $14 billion in sales a year, is a shining example of protein therapy. . . .”
- Moderna aims at doing an end run around that technology with the injection of mRNA (messenger RNA) or DNA. This is a risky technology: “ . . . . Moderna’s technology promised to subvert the whole field, creating therapeutic proteins inside the body instead of in manufacturing plants. The key: harnessing messenger RNA, or mRNA. . . . . It’s highly risky. Big pharma companies had tried similar work and abandoned it because it’s exceedingly hard to get RNA into cells without triggering nasty side effects. . . . .”
- CEO Bancel has maintained the company’s opaque professional culture, mixed with high-profile media promotion: “ . . . . Under Bancel, Moderna has been loath to publish its work in Science or Nature, but enthusiastic to herald its potential on CNBC and CNN, taking part in segments on the world’s most disruptive companiesand the potential ‘cure for cancer.’ . . .”
- Moderna had draconian attitude toward employees from its inception: “ . . . . From the beginning, Bancel made clear that Moderna’s science simply had to work. And that anyone who couldn’t make it work didn’t belong. The early Moderna was a chaotic, unpredictable workplace, according to former employees. One recalls finding himself out of a job when a quick-turnaround experiment failed to pan out. Another helped train a group of new hires only to realize they were his replacements. . . .”
- Joe Bolen exemplified the treatment Moderna meted out: “ . . . . Most stunning to employees was the abrupt departure of Joseph Bolen, who came aboard in 2013 to lead Moderna’s R&D efforts. Bolen was a big-name hire in biotech circles, an experienced chief scientific officer who had guided Millennium Pharmaceuticals to FDA approval for a blockbuster cancer drug. . . ‘No scientist in his right mind would leave that job unless there was something wrong with the science or the personnel,’ said a person close to the company at the time.’ . . .”
- Bolen had company: “ . . . . Bolen wasn’t alone. Chief Information Officer John Reynders joined in 2013 to make Moderna what he called the world’s ‘first fully digital biotech,‘only to step down a year later. Michael Morin, brought in to lead Moderna’s scientific efforts in cancer in 2014, lasted less than 18 months. As did Greg Licholai, hired in 2015 to direct the company’s projects in rare diseases. The latter two key leadership positions remain unfilled. . . .”
- The explanation of CFO Lorence Kim is less than reassuring from the standpoint of product safety and reliability: “ . . . . ‘We force everyone to grow with the company at unprecedented speed,’ Moderna Chief Financial Officer Lorence Kim said. ‘Some people grow with the company; others don’t.’ . . .”
- Beginning in 2013, Moderna partnered with a series of pharmaceutical giants, including AstraZeneca, which has been selected to develop a Covid-19 vaccine: “ . . . . That’s when Moderna — which had just 25 employees — signed a staggering $240 million partnership with UK pharmaceutical giant AstraZeneca. It was the most money pharma had ever spent on drugs that had not yet been tested in humans. . . .”
- The firm has been lavishly capitalized: “ . . . . In early 2015, Moderna disclosed a $450 million financing round, the largest ever for a private biotech company. This month, the company broke its own record, raising another $474 million. . . . Though it has yet to reveal data from a single clinical trial, Moderna is now valued at $4.7 billion, according to Pitchbook. . . .”
- Initially, Moderna aimed at developing products that would be administered for a period of years: “ . . . . From the start, Moderna heralded its ability to produce proteins within cells, which could open up a world of therapeutic targets unreachable by conventional drugs. The most revolutionary treatments, which could challenge the multibillion-dollar market for protein therapy, would involve repeated doses of mRNA over many years, so a patient’s body continued to produce proteins to keep disease at bay. . . .”
- Instead of producing treatments that would be administered over a period of years, the company focused on vaccines: “ . . . . But Moderna’s first human trials aren’t so ambitious, focusing instead on the crowded field of vaccines, where the company has only been working since 2014. . . . The choice to prioritize vaccines came as a disappointment to many in the company, according to a former manager. The plan had been to radically disrupt the biotech industry, the manager said, so ‘why would you start with a clinical program that has very limited upside and lots of competition?’” . . . .”
- The answer to Moderna’s focus on vaccines may be due to issues of product safety: “ . . . Delivery — actually getting RNA into cells — has long bedeviled the whole field. On their own, RNA molecules have a hard time reaching their targets. They work better if they’re wrapped up in a delivery mechanism, such as nanoparticles made of lipids. But those nanoparticles can lead to dangerous side effects, especially if a patient has to take repeated doses over months or years. . . .”
- Vaccines will only administer mRNA at the time of vaccination, rather than over a long period of time: “ . . . . ‘I would say that mRNA is better suited for diseases where treatment for short duration is sufficiently curative, so the toxicities caused by delivery materials are less likely to occur,’ said Katalin Karikó, a pioneer in the field who serves as a vice president at BioNTech. . . That makes vaccines the lowest hanging fruit in mRNA, said Franz-Werner Haas, CureVac’s chief corporate officer. ‘From our point of view, it’s obvious why [Moderna] started there,’ he said.’ . . .”
- Moderna’s explanation for its focus on vaccines is not reassuring—the speed with which it can proceed to human trials. The firm’s secrecy has generated alarm: “ . . . . Moderna said it prioritized vaccines because they presented the fastest path to human trials, not because of setbacks with other projects. ‘The notion that [Moderna] ran into difficulties isn’t borne in reality,’ said [Chairman of the board Noubar] Afeyan. But this is where Moderna’s secrecy comes into play: Until there’s published data, only the company and its partners know what the data show. Everyone outside is left guessing — and, in some cases, worrying that Moderna won’t live up to its hype. . . .”
- Moderna applies software and a business model derived from Tesla, Amazon and Uber: “ . . . . Moderna has pioneered an automated system modeled on the software Tesla uses to manage orders, Bancel said: Scientists simply enter the protein they want a cell to express, and testable mRNA arrives within weeks. . . . That has always been part of the plan, former employees said, pointing to Bancel’s fascination with the tech industry. Uber and Amazon were not the first to come up with their respective business ideas, but they were the ones that built enough scale to ward off competition. And Moderna is positioning itself to do the same in mRNA. . . .”
Moncef Slaoui
Moncef Slaoui’s optimistic statement on the Friday before the Monday announcement, presents important context for Moderna’s Monday announcement. That announcement moved markets based on inadequate data. “Operation Warp Speed” (headed by Slaoui) suggests that candidate Trump is very interested in those preliminary results as well.
Elizabeth Warren scored Slaoui’s conflict of interest–a consideration that will be discussed at length: ” . . . . Following Moncef Slaoui’s Friday appointment as a co-leader of the Warp Speed program, he’s set to sell about 155,000 shares in Moderna, according to press reports. They were worth an estimated $10 million Friday, but after Monday’s stock run-up on positive early data, they’re now valued at about $12.4 million. . . . Following Slaoui’s selection, Sen. Elizabeth Warren tweeted that it’s a ‘huge conflict of interest’ for him to keep the Moderna stock as he assumes the new role. She said he should ‘divest immediately.’ In a now-deleted tweet, Slaoui responded that there ‘is no conflict of interest, and there never has been,’ Business Insider reports. . . .”
Even after agreeing to sell his Moderna stock, Slaoui’s investments raise alarming questions–note that he is a “venture capitalist” and a longtime former executive at Glaxo-Smithkline:
- The circumstances of his appointment will permit him to avoid scrutiny: ” . . . . In agreeing to accept the position, Dr. Slaoui did not come on board as a government employee. Instead, he is on a contract, receiving $1 for his service. That leaves him exempt from federal disclosure rules that would require him to list his outside positions, stock holdings and other potential conflicts. And the contract position is not subject to the same conflict-of-interest laws and regulations that executive branch employees must follow. . . .”
- He will retain a great deal of Glaxo-Smithkline stock: ” . . . . He did not say how much his GSK shares were worth. When he left the company in 2017, he held about [500,000 in Western Print Edition] 240,000 shares and share equivalents, according to the drug company’s annual report and an analysis by the executive compensation firm Equilar. . . .”
- Further analysis of Slaoui’s position deepens concern about the integrity of the process: ” . . . . ‘This is basically absurd,’ said Virginia Canter, who is chief ethics counsel for Citizens for Responsibility and Ethics in Washington. ‘It allows for no public scrutiny of his conflicts of interest.’ Ms. Canter also said federal law barred government contractors from supervising government employees. . . . Ms. Canter, a former ethics lawyer in the Obama and Clinton administrations, the Securities and Exchange Commission and other agencies, pointed out that GSK’s vaccine candidate with Sanofi could wind up competing with other manufacturers vying for government approval and support. ‘If he retains stock in companies that are investing in the development of a vaccine, and he’s involved in overseeing this process to select the safest vaccine to combat Covid-19, regardless of how wonderful a person he is, we can’t be confident of the integrity of any process in which he is involved,’ Ms. Canter said. In addition, his affiliation with Medicxi could complicate matters: Two of its investors are GSK and a division of Johnson & Johnson, which is also developing a potential vaccine. . . .”
Moderna stands to make billions of dollars if their vaccine goes to market:
- ” . . . . What investors are betting on, for Moderna and others developing vaccines against the SARS-CoV‑2 virus, is that a third of the developed world’s population will get vaccinated every year. That could amount to a $10 billion annual business, at an estimated price of $30 per vaccination. . . .”
- ” . . . . Morgan Stanley analysts this past weekend suggested that pricing might start at $5 to $10 a dose during this first pandemic crisis, then rise to a range of $13 to $30 for preventive doses in future years. But at BMO Capital Markets, analyst George Farmer speculated that Moderna could start charging $125 per treatment in the U.S. market and raise that price over time to $200. . . . ”
We close the program with a reminder of the extent to which federal funding drives the value of Moderna: ” . . . . ‘Instead of waiting for the data and then scaling up with manufacturing process … we can make as many doses as we can. We are doing both in parallel,’ he said. The company plans to hire up to 150 people to support the effort. Bancel said the company ‘couldn’t have done this’ without the funding commitment from the Biomedical Advanced Research and Development Authority, which is part of the Department of Health and Human Services. . . .”
1a. We begin by Introducing the topic of Moderna’s SARS Cov‑2 vaccine as a money maker for both Moderna and as a driver for the market as a whole, we note last Monday’s announcement which generated a major boost in the value of Moderna’s stock and a strong, general rally. The latter apparently stems from optimism that a sucessful vaccine will alleviate the economic damage from Covid-19:
. . . . The promising early news sent Moderna’s stock soaring by more than 25 percent on Monday afternoon and helped drive Wall Street to its best day in six weeks. . . . Trading on Monday had all of the characteristics of a rally focused on prospects for a return to normal: The S&P 500 rose more than 3 percent; stock benchmarks in Europe were 4 percent to 6 percent higher; and oil prices also jumped. Among the best performers in the S&P 500 were travel-related companies, like United Airlines, Expedia Group and Marriott International. . . .
1b. A MarketWatch piece about the rapid fluctuation of Moderna’s stock underscores the significance of the timing of an announcement casting Moderna’s vaccine trial in overly optimistic light:
- Moderna’s CEO (Stephen Bancel) and CFO (Lorence Kim) both sold stock on Friday, in accordance with prearranged transactions. Bear in mind, that (as discussed in FTR #1130), Moderna’s stock was trading at $23.46 at the beginning of the year, and the company–which has never marketed a vaccine–was the beneficiary of $483 million dollars in federal funding earlier in the year.) ” . . . . On Friday, Bancel sold 11,046 shares at a weighted average price of $65.56 for about $724,200, as part of a predetermined trading plan adopted Dec. 28, 2018, according to a Form 4 filing with the Securities and Exchange Commission. He also disposed of 1,577 shares as part of a ‘bona fide’ gift. . . . Also, on Friday, Kim sold 20,000 shares at a weighted average price of $65.53 for about $1.31 million, as part of a predetermined trading plan. . . .”
- Kim also simultaneously bought and sold shares of his firm for a net profit of $16.79 million on Monday, the day of an overly optimistic announcement by Moderna. The fortuitously timed Moderna announcement made the firm’s CFO roughly $4 million: ” . . . . On Monday, he [Kim] exercised options to buy 241,000 shares at a weighted average price of $12.45 for about $3 million, also as part of a predetermined plan. At the same time, Kim executed sales of 241,000 shares, at a weighted average price of $82.12 for about $19.79 million. That means Kim netted about $16.79 million on the simultaneous buy and sale of shares. . . . with Monday’s stock price surge following the announcement of early data on its vaccine candidate potentially adding $4 million to Kim’s coffers. . . .”
- The above-referenced announcement by Moderna led to a dramatic increase in Moderna’s stock and boosted the market as a whole. Moderna announced that evening that it would sell $1.34 billion in stock to help its vaccine operation: ” . . . . Shares of Moderna closed at a record high of $80.00 on Monday after the company released a slice of positive interim clinical data from the first phase of its COVID-19 vaccine trial. That night it announced it would sell $1.34 billion in stock to help fund manufacturing costs associated with the experimental COVID-19 vaccine. . . .”
- Moderna’s stock nosedived at the end of the trading day on Tuesday, due to a critical article from Stat News: ” . . . . The stock took a nose dive on Tuesday, closing at $71.67, likely due in some degree to a Stat News story that questioned a lack of clinical clarity in the data it provided to investors. . . .”
- Moderna’s announcement was critically assessed by Stat News, which pointed out that the results were incomplete at best: ” . . . . In a clinical-trial data disclosure on Monday, Moderna shared that eight out of 45 participants in its COVID-19 vaccine study developed neutralizing antibodies, a decision that Stat’s Helen Branswell described as a ‘reason for caution.’ It didn’t share information about the immune response to the experimental vaccine in the remaining 37 participants. . . .”
- Nonetheless, Moderna’s stock–bolstered by government investment–has been on a dramatic upward swing: ” . . . . The company’s stock was up 3.8% in trading on Wednesday. Year-to-date, it has soared 270.2%, even though the company has no approved products. . . .”
Wall Street analysts largely view the clinical-trial data released by Moderna, however limited, as a positive
Investors in Moderna Inc., the preclinical biotechnology company developing one of the front-running COVID-19 vaccine candidates in the U.S., may be facing a volatile ride through the clinical trial process.
Shares of Moderna closed at a record high of $80.00 on Monday after the company released a slice of positive interim clinical data from the first phase of its COVID-19 vaccine trial. That night it announced it would sell $1.34 billion in stock to help fund manufacturing costs associated with the experimental COVID-19 vaccine. The stock took a nose dive on Tuesday, closing at $71.67, likely due in some degree to a Stat News story that questioned a lack of clinical clarity in the data it provided to investors.
The company’s stock was up 3.8% in trading on Wednesday. Year-to-date, it has soared 270.2%, even though the company has no approved products. In 2019, it had $60 million in revenue that came from collaborations and grants.
…
In a clinical-trial data disclosure on Monday, Moderna shared that eight out of 45 participants in its COVID-19 vaccine study developed neutralizing antibodies, a decision that Stat’s Helen Branswell described as a “reason for caution.” It didn’t share information about the immune response to the experimental vaccine in the remaining 37 participants.
Moderna, however, said that the full data from the trial will be published by the National Institute for Allergy and Infectious Diseases (NIAID), its sponsor for the study.
The company had also already disclosed that the Food and Drug Administration (FDA) has given the go-ahead for the company to proceed with the second phase of the clinical trial for its mRNA vaccine candidate, set to begin before the end of June.
Despite the critics cited in the Stat News article, Wall Street analysts largely view the clinical-trial data released by Moderna, however limited, as a positive.
“While samples are not yet available for remaining participants, and we lack specifics on the exact levels of binding antibodies, we view this data as demonstrative of early signs of efficacy,” Goldman Sachs analysts wrote in an investor note on Monday.
Medical experts and analysts have also raised questions about the lack of complete data from Gilead Sciences Inc.’s late-stage study for remdesivir, which was also conducted with the NIAID.) So far, only the topline results from that trial have been shared publicly, though that was enough to inform the emergency use authorization granted by the FDA earlier this month, at least according to the FDA’s letter announcing the EUA.
“We need to see all that data, the publication,” Dr. Eric Topol, a cardiologist and director of the Scripps Research Translational Institute, said by email on May 1. “But I do believe the drug has efficacy based on what we now know, it’s just not that potent.”
Beyond lingering questions about access to the complete Phase 1 clinical trial data set for the investigational vaccine, Moderna’s splashy offering on Monday night aiming to sell about $1.3 billion in stock may also have contributed to the dive on Tuesday.
The company disclosed late Tuesday that Chief Executive Stéphane Bancel and Chief Financial Officer Lorence Kim sold stock recently, with Monday’s stock price surge following the announcement of early data on its vaccine candidate potentially adding $4 million to Kim’s coffers.
On Friday, Bancel sold 11,046 shares at a weighted average price of $65.56 for about $724,200, as part of a predetermined trading plan adopted Dec. 28, 2018, according to a Form 4 filing with the Securities and Exchange Commission. He also disposed of 1,577 shares as part of a “bona fide” gift.
Also, on Friday, Kim sold 20,000 shares at a weighted average price of $65.53 for about $1.31 million, as part of a predetermined trading plan. On Monday, he exercised options to buy 241,000 shares at a weighted average price of $12.45 for about $3 million, also as part of a predetermined plan. At the same time, Kim executed sales of 241,000 shares, at a weighted average price of $82.12 for about $19.79 million. That means Kim netted about $16.79 million on the simultaneous buy and sale of shares.
If Kim had executed Monday’s trades on Friday, before the coronavirus vaccine-related stock rally, he might have netted $12.79 million, or about $4 million less.
Morgan Stanley analysts on Wednesday set a price target of $90.00 for Moderna, noting that they expect the company will sell an estimated 1.5 billion doses during the pandemic and about 150 million doses each year after that. “We are positive on the early data,” they wrote.
Moderna’s market capitalization is roughly $27.4 billion, up from about $6.4 billion on Jan. 2.
The S&P 500 is down 9.3% year-to-date.
2a. There are serious questions about the substance of Moderna’s statement:
- Moderna’s much touted report on its vaccine—which triggered an upsurge in the markets on Monday—appears to have been incomplete, at best, and purposefully deceptive, at worst. “ . . . . While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data.. . . . If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words. Even the figures the company did release don’t mean much on their own, because critical information — effectively the key to interpreting them — was withheld. . . .”
- Part of the reason for alarm and skepticism concerns the behavior of the NIAID—whose director is Anthony Fauci: “ . . . . The National Institute for Allergy and Infectious Diseases has partnered with Moderna on this vaccine. Scientists at NIAID made the vaccine’s construct, or prototype, and the agency is running the Phase 1 trial. This week’s Moderna readout came from the earliest of data from the NIAID-led Phase 1. NIAID doesn’t hide its light under a bushel. The institute generally trumpets its findings, often offering director Anthony Fauci . . . or other senior personnel for interviews. But NIAID did not put out a press release Monday and declined to provide comment on Moderna’s announcement. . . .”
- To begin with, Moderna’s announcement was only statistically substantive for 8 of the 45 volunteer subjects: “ . . . . The company’s statement led with the fact that all 45 subjects (in this analysis) who received doses of 25 micrograms (two doses each), 100 micrograms (two doses each), or a 250 micrograms (one dose) developed binding antibodies. Later, the statement indicated that eight volunteers — four each from the 25-microgram and 100-microgram arms — developed neutralizing antibodies. Of the two types, these are the ones you’d really want to see. We don’t know results from the other 37 trial participants. . . .”
- It is possible that neutralizing antibodies may have been developed in the 37 test subjects whose data was not released because the testing process is exacting. Still the statement warrants caution, at the least. “ . . . . This doesn’t mean that they didn’t develop neutralizing antibodies.Testing for neutralizing antibodies is more time-consuming than other antibody tests and must be done in a biosecurity level 3 laboratory. Moderna disclosed the findings from eight subjects because that’s all it had at that point. Still, it’s a reason for caution . . . .”
- In addition, the age of the subjects was not released and that is relevant. “ . . . . Separately, while the Phase 1 trial included healthy volunteers ages 18 to 55 years, the exact ages of these eight people are unknown. If, by chance, they mostly clustered around the younger end of the age spectrum, you might expect a better response to the vaccine than if they were mostly from the senior end of it. And given who is at highest risk from the SARS-CoV‑2 coronavirus, protecting older adults is what Covid-19 vaccines need to do. . . .”
- In addition, there was no data released as to the durability of the neutralizing antibodies. If, for the sake of argument, they are not long-lasting, the utility of the vaccine is negligible. “ . . . . The report of neutralizing antibodies in subjects who were vaccinated comes from blood drawn two weeks after they received their second dose of vaccine. Two weeks. ‘That’s very early. We don’t know if those antibodies are durable,’ said Anna Durbin, a vaccine researcher at Johns Hopkins University. . . .”
- Still another point of contention/alarm concerns the variability in neutralizing antibodies among recovered patients: “ . . . . But studies have shown antibody levels among people who have recovered from the illness vary enormously; the range that may be influenced by the severity of a person’s disease. John ‘Jack’ Rose, a vaccine researcher from Yale University, pointed STAT to a study from China that showed that, among 175 recovered Covid-19 patients studied, 10 had no detectable neutralizing antibodies. Recovered patients at the other end of the spectrum had really high antibody levels. So though the company said the antibody levels induced by vaccine were as good as those generated by infection, there’s no real way to know what that comparison means. . . .”
- It is less than encouraging that Moderna disclosed that more relevant data will be disclosed in a report to be released in conjunction with NIAID: “ . . . . STAT asked Moderna for information on the antibody levels it used as a comparator. The response: That will be disclosed in an eventual journal article from NIAID, which is part of the National Institutes of Health. . . .”
- Ann Durbin was struck by the wording of Moderna’s release: “ . . . . Durbin was struck by the wording of the company’s statement, pointing to this sentence: ‘The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.’ ‘I thought: Generally? What does that mean?’ Durbin said. Her question, for the time being, can’t be answered. . . .”
- Jack Rose commented on the opaque nature of Moderna’s release: “. . . . Rose said the company should disclose the information. ‘When a company like Moderna with such incredibly vast resources says they have generated SARS‑2 neutralizing antibodies in a human trial, I would really like to see numbers from whatever assay they are using,’ he said. . . .”
- To date, Moderna issues press releases, not papers that can be vetted by the scientific community: “ . . . . It doesn’t publish on its work in scientific journals. What is known has been disclosed through press releases. That’s not enough to generate confidence within the scientific community. ‘My guess is that their numbers are marginal or they would say more,’ Rose said about the company’s SARS‑2 vaccine, echoing a suspicion that others have about some of the company’s other work. ‘I do think it’s a bit of a concern that they haven’t published the results of any of their ongoing trials that they mention in their press release. They have not published any of that,’ Durbin noted. . . .”
Heavy hearts soared Monday with news that Moderna’s Covid-19 vaccine candidate — the frontrunner in the American market — seemed to be generating an immune response in Phase 1 trial subjects. The company’s stock valuation also surged, hitting $29 billion, an astonishing feat for a company that currently sells zero products.
But was there good reason for so much enthusiasm? Several vaccine experts asked by STAT concluded that, based on the information made available by the Cambridge, Mass.-based company, there’s really no way to know how impressive — or not — the vaccine may be.
While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data. That’s important: If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words.
Even the figures the company did release don’t mean much on their own, because critical information — effectively the key to interpreting them — was withheld.
…
The silence of the NIAID
The National Institute for Allergy and Infectious Diseases has partnered with Moderna on this vaccine. Scientists at NIAID made the vaccine’s construct, or prototype, and the agency is running the Phase 1 trial. This week’s Moderna readout came from the earliest of data from the NIAID-led Phase 1.
NIAID doesn’t hide its light under a bushel. The institute generally trumpets its findings, often offering director Anthony Fauci — who, fair enough, is pretty busy these days — or other senior personnel for interviews.
But NIAID did not put out a press release Monday and declined to provide comment on Moderna’s announcement.
The n = 8 thing
The company’s statement led with the fact that all 45 subjects (in this analysis) who received doses of 25 micrograms (two doses each), 100 micrograms (two doses each), or a 250 micrograms (one dose) developed binding antibodies.
Later, the statement indicated that eight volunteers — four each from the 25-microgram and 100-microgram arms — developed neutralizing antibodies. Of the two types, these are the ones you’d really want to see.
We don’t know results from the other 37 trial participants. This doesn’t mean that they didn’t develop neutralizing antibodies. Testing for neutralizing antibodies is more time-consuming than other antibody tests and must be done in a biosecurity level 3 laboratory. Moderna disclosed the findings from eight subjects because that’s all it had at that point. Still, it’s a reason for caution.
Separately, while the Phase 1 trial included healthy volunteers ages 18 to 55 years, the exact ages of these eight people are unknown. If, by chance, they mostly clustered around the younger end of the age spectrum, you might expect a better response to the vaccine than if they were mostly from the senior end of it. And given who is at highest risk from the SARS-CoV‑2 coronavirus, protecting older adults is what Covid-19 vaccines need to do.
There’s no way to know how durable the response will be
The report of neutralizing antibodies in subjects who were vaccinated comes from blood drawn two weeks after they received their second dose of vaccine.
Two weeks.
“That’s very early. We don’t know if those antibodies are durable,” said Anna Durbin, a vaccine researcher at Johns Hopkins University.
There’s no real way to contextualize the findings
Moderna stated that the antibody levels seen were on a par with — or greater than, in the case of the 100-microgram dose — those seen in people who have recovered from Covid-19 infection.
But studies have shown antibody levels among people who have recovered from the illness vary enormously; the range that may be influenced by the severity of a person’s disease. John “Jack” Rose, a vaccine researcher from Yale University, pointed STAT to a study from China that showed that, among 175 recovered Covid-19 patients studied, 10 had no detectable neutralizing antibodies. Recovered patients at the other end of the spectrum had really high antibody levels.
So though the company said the antibody levels induced by vaccine were as good as those generated by infection, there’s no real way to know what that comparison means.
STAT asked Moderna for information on the antibody levels it used as a comparator. The response: That will be disclosed in an eventual journal article from NIAID, which is part of the National Institutes of Health.
“The convalescent sera levels are not being detailed in our data readout, but would be expected in a downstream full data exposition with NIH and its academic collaborators,” Colleen Hussey, the company’s senior manager for corporate communications, said in an email.
Durbin was struck by the wording of the company’s statement, pointing to this sentence: “The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.”
“I thought: Generally? What does that mean?” Durbin said. Her question, for the time being, can’t be answered.
Rose said the company should disclose the information. “When a company like Moderna with such incredibly vast resources says they have generated SARS‑2 neutralizing antibodies in a human trial, I would really like to see numbers from whatever assay they are using,” he said.
Moderna’s approach to disclosure
The company has not yet brought a vaccine to market, but it has a variety of vaccines for infectious diseases in its pipeline. It doesn’t publish on its work in scientific journals. What is known has been disclosed through press releases. That’s not enough to generate confidence within the scientific community.
“My guess is that their numbers are marginal or they would say more,” Rose said about the company’s SARS‑2 vaccine, echoing a suspicion that others have about some of the company’s other work.
“I do think it’s a bit of a concern that they haven’t published the results of any of their ongoing trials that they mention in their press release. They have not published any of that,” Durbin noted.
Still, she characterized herself as “cautiously optimistic” based on what the company has said so far.
“I would like to see the data to make my own interpretation of the data. But I think it is at least encouraging that we’ve seen immune responses with this RNA vaccine that we haven’t seen with previous RNA vaccines for other pathogens. Whether it’s going to be enough, we don’t know,” Durbin said.
Moderna has been more forthcoming with data on at least one of its other vaccine candidates. In a statement issued in January about a Phase 1 trial for its cytomegalovirus (CMV) vaccine, it quantified how far over baseline measures antibody levels rose in vaccines.
2a. The following article from Nature Reviews Immunology warns us of a potential safety issue with the SARS-CoV‑2 vaccine: In the original SARS outbreak, we learned that if someone develops antibodies–but not at a high enough level to neutralize the infection–that can actually make that infection more severe. This process is known as antibody-dependent enhancement (ADE). This only happens when the neutralizing antibody levels are below some threshold.
If a vaccine induced an immune response that isn’t high enough it could actually make the eventual infections even worse. This has been demonstrated in Mice with SARS vaccines. As the authors also note, there’s some evidence aged animals might have a harder time generating the required levels of antibodies after vaccination. So it’s possible to have a vaccine that protects the young and actually makes the elderly more vulnerable:
There is a desperate need for effective therapies and vaccines for SARS-CoV‑2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked.
…
The quality and quantity of the antibody response dictates functional outcomes. High-affinity antibodies can elicit neutralization by recognizing specific viral epitopes (Fig.1a). Neutralizing antibodies are defined in vitro by their ability to block viral entry, fusion or egress. In vivo, neutralizing antibodies can function without additional mediators, although the Fc region is required for neutralization of influenza virus2. In the case of SARS-CoV, viral docking on ACE2 on host cells is blocked when neutralizing antibodies, for example, recognize the receptor-binding domain (RBD) on the spike (S) protein3. S protein-mediated viral fusion can be blocked by neutralizing antibodies targeting the heptad repeat 2 (HR2) domain3. In addition, neutralizing antibodies can interact with other immune components, including complement, phagocytes and natural killer cells. These effector responses can aid in pathogen clearance, with engagement of phagocytes shown to enhance antibody-mediated clearance of SARS-CoV4. However, in rare cases, pathogen-specific antibodies can promote pathology, resulting in a phenomenon known as antibody-dependent enhancement (ADE).
Fig. 1: Potential outcomes of antibody response to coronavirus.
Antibody-dependent enhancement
Although antibodies are generally protective and beneficial, the ADE phenomenon is documented for dengue virus and other viruses. In SARS-CoV infection, ADE is mediated by the engagement of Fc receptors (FcRs) expressed on different immune cells, including monocytes, macrophages and B cells5,6. Pre-existing SARS-CoV-specific antibodies may thus promote viral entry into FcR-expressing cells (Fig. 1b). This process is independent of ACE2 expression and endosomal pH and proteases, suggesting distinct cellular pathways of ACE2-mediated and FcR-mediated viral entry6. There is no evidence that ADE facilitates the spread of SARS-CoV in infected hosts. In fact, infection of macrophages through ADE does not result in productive viral replication and shedding7. Instead, internalization of virus–antibody immune complexes can promote inflammation and tissue injury by activating myeloid cells via FcRs5. Virus introduced into the endosome through this pathway will likely engage the RNA-sensing Toll-like receptors (TLRs) TLR3, TLR7 and TLR8 (Fig. 1c). Uptake of SARS-CoV through ADE in macrophages led to elevated production of TNF and IL‑6 (ref.5). In mice infected with SARS-CoV, ADE was associated with decreased levels of the anti-inflammatory cytokines IL-10 and TGFß and increased levels of the pro-inflammatory chemokines CCL2 and CCL3 (ref.8). Furthermore, immunization of non-human primates with a modified vaccinia Ankara (MVA) virus encoding the full-length S protein of SARS-CoV promoted activation of alveolar macrophages, leading to acute lung injury9.
Protective versus pathogenic antibodies
Multiple factors determine whether an antibody neutralizes a virus and protects the host or causes ADE and acute inflammation. These include the specificity, concentration, affinity and isotype of the antibody. Viral vector vaccines encoding SARS-CoV S protein and nucleocapsid (N) protein provoke anti‑S and anti‑N IgG in immunized mice, respectively, to a similar extent. However, upon re-challenge, N protein-immunized mice show significant upregulation of pro-inflammatory cytokine secretion, increased neutrophil and eosinophil lung infiltration, and more severe lung pathology8. Similarly, antibodies targeting different epitopes on the S protein may vary in their potential to induce neutralization or ADE. For example, antibodies reactive to the RBD domain or the HR2 domain of the S protein induce better protective antibody responses in non-human primates, whereas antibodies specific for other S protein epitopes can induce ADE10. In vitro data suggest that for cells expressing FcRs, ADE occurs when antibody is present at a low concentration but dampens at the high-concentration range. Meanwhile, increasing antibody concentrations promotes SARS-CoV neutralization by blocking viral entry into host cells6. For other viruses, high-affinity antibodies capable of blocking receptor binding tend to not induce ADE.
In the ‘multiple hit’ model of neutralization, the virus-blocking effect correlates with the number of antibodies coating the virion, which is collectively affected by antibody concentration and affinity11. Monoclonal antibodies with higher affinity for the envelope (E) protein of West Nile Virus (WNV) induced better protection in mice receiving a lethal dose of WNV11. For a given concentration of antibody and a specific targeting domain, the stoichiometry of antibody engagement on a virion is dependent on the strength of interaction between antibody and antigen. ADE is induced when the stoichiometry is below the threshold for neutralization. Therefore, higher affinity antibodies can reach that threshold at a lower concentration and mediate better protection11.
Antibody isotypes control their effector functions. IgM is considered more pro-inflammatory as it activates complement efficiently. IgG subclasses modulate immune responses via the engagement of different FcRs. Most FcγRs signal through ITAMs, but FcγRIIb contains an ITIM on its cytoplasmic tail that mediates an anti-inflammatory response. Ectopic expression of FcγRIIa and FcγRIIb, but not of FcγRI or FcγRIIIa, induced ADE of SARS-CoV infection6. Allelic polymorphisms in FcγRIIa are associated with SARS pathology, and individuals with an FcγRIIa isoform that binds to both IgG1 and IgG2 were found to develop more severe disease than individuals with Fcγthat only binds to IgG2 (ref.12).
Vaccine approaches
It is crucial to determine which vaccines and adjuvants can elicit protective antibody responses to SARS-CoV‑2. Previous studies have shown that the immunization of mice with inactivated whole SARS-CoV13, the immunization of rhesus macaques9 with MVA-encoded S protein and the immunization of mice with DNA vaccine encoding full-length S protein14 could induce ADE or eosinophil-mediated immunopathology to some extent, possibly owing to low quality and quantity of antibody production. Additionally, we need to consider whether a vaccine is safe and effective in aged hosts. For instance, double-inactivated SARS-CoV vaccine failed to induce neutralizing antibody responses in aged mice13. Furthermore, although an alum-adjuvanted double-inactivated SARS-CoV vaccine elicited higher antibody titres in aged mice, it skewed the IgG subclass toward IgG1 instead of IgG2, which was associated with a T helper 2 (TH2)-type immune response, enhanced eosinophilia and lung pathology13. By contrast, studies in mice showed that subunit or peptide vaccines that focus the antibody response against specific epitopes within the RBD of the S protein conferred protective antibody responses3. In addition, live attenuated SARS-CoV vaccine induced protective immune responses in aged mice15. Routes of vaccine administration can further affect vaccine efficacy. Compared with the intramuscular route, intranasal administration of a recombinant adeno-associated virus vaccine encoding SARS-CoV RBD induced significantly higher titres of mucosal IgA in the lung and reduced lung pathology upon challenge with SARS-CoV3.
Concluding remarks
There are now multiple vaccine candidates (including nucleic acid vaccines, viral vector vaccines and subunit vaccines) in the preclinical and clinical trial stages as researchers and institutes from all over the world come together to accelerate the development of a SARS-CoV‑2 vaccine. Recent studies of antibody responses in patients with COVID-19 have associated higher titres of anti‑N IgM and IgG at all time points following the onset of symptoms with a worse disease outcome16. Moreover, higher titres of anti‑S and anti‑N IgG and IgM correlate with worse clinical readouts and older age17, suggesting potentially detrimental effects of antibodies in some patients. However, 70% of patients who recovered from mild COVID-19 had measurable neutralizing antibodies that persisted upon revisit to the hospital18. Thus, insights gained from studying the antibody features that correlate with recovery as opposed to worsening of disease will inform the type of antibodies to assess in vaccine studies. We argue that ADE should be given full consideration in the safety evaluation of emerging candidate vaccines for SARS-CoV‑2. In addition to vaccine approaches, monoclonal antibodies could be used to tackle this virus. Unlike vaccine-induced antibodies, monoclonal antibodies can be engineered with molecular precision. Safe and effective neutralizing antibodies could be produced on a mass-scale for delivery to populations across the world in the coming months. . . .
3. A 2016 STAT News article about Moderna highlights a number of areas of concern, given the speed and relatively opaque nature of the potential introduction of its Covid-19 vaccine. The financing of the company by DARPA, and Moncef Slaoui’s joining with Four Star General Perna (elevated by the Chairman of the Joint Chiefs of Staff, General Mark A. Milley) are of additional concern.
- As of 2016, Moderna had the largest valuation of any private biotech firm and former employees felt that Moderna prized money over science. Note that, as will be reviewed later in the program, its stock has risen exponentially as a result of the injection of hundreds of millions of dollars. Bear in mind that Moderna has also been underwritten by DARPA. “ . . . . Moderna is worth more than any other private biotech in the US, and former employees said they felt that Bancel prized the company’s ever-increasing valuation, now approaching $5 billion, over its science. . . .”
- Moderna has maintained a culture of secrecy, which in 2016, applied to the first two products undergoing phase 1 trials: “ . . . . Moderna just moved its first two potential treatments — both vaccines — into human trials. In keeping with the culture of secrecy, though, executives won’t say which diseases the vaccines target, and they have not listed the studies on the public federal registry, ClinicalTrials.gov. Listing is optional for Phase 1 trials, which are meant to determine if a drug is safe, but most companies voluntarily disclose their work. . . .”
- Protein therapy has been a driving economic and therapeutic factor in the pharmaceutical business: “ . . . . For decades, companies have endeavored to craft better and better protein therapies, leading to new treatments for cancer, autoimmune disorders, and rare diseases. Such therapies are costly to produce and have many limitations, but they’ve given rise to a multibillion-dollar industry. The anti-inflammatory Humira, the world’s top drug at $14 billion in sales a year, is a shining example of protein therapy. . . .”
- Moderna aims at doing an end run around that technology with the injection of mRNA (messenger RNA) or DNA. This is a risky technology: “ . . . . Moderna’s technology promised to subvert the whole field, creating therapeutic proteins inside the body instead of in manufacturing plants. The key: harnessing messenger RNA, or mRNA. . . . . It’s highly risky. Big pharma companies had tried similar work and abandoned it because it’s exceedingly hard to get RNA into cells without triggering nasty side effects. . . . .”
- CEO Bancel has maintained the company’s opaque professional culture, mixed with high-profile media promotion: “ . . . . Under Bancel, Moderna has been loath to publish its work in Science or Nature, but enthusiastic to herald its potential on CNBC and CNN, taking part in segments on the world’s most disruptive companiesand the potential ‘cure for cancer.’. . .”
- Moderna had draconian attitude toward employees from its inception: “ . . . . From the beginning, Bancel made clear that Moderna’s science simply had to work. And that anyone who couldn’t make it work didn’t belong. The early Moderna was a chaotic, unpredictable workplace, according to former employees. One recalls finding himself out of a job when a quick-turnaround experiment failed to pan out. Another helped train a group of new hires only to realize they were his replacements. . . .”
- Joe Bolen exemplified the treatment Moderna meted out: “ . . . . Most stunning to employees was the abrupt departure of Joseph Bolen, who came aboard in 2013 to lead Moderna’s R&D efforts. Bolen was a big-name hire in biotech circles, an experienced chief scientific officer who had guided Millennium Pharmaceuticals to FDA approval for a blockbuster cancer drug. . . ‘No scientist in his right mind would leave that job unless there was something wrong with the science or the personnel,’ said a person close to the company at the time.’ . . .”
- Bolen had company: “ . . . . Bolen wasn’t alone. Chief Information Officer John Reynders joined in 2013 to make Moderna what he called the world’s ‘first fully digital biotech,‘only to step down a year later. Michael Morin, brought in to lead Moderna’s scientific efforts in cancer in 2014, lasted less than 18 months. As did Greg Licholai, hired in 2015 to direct the company’s projects in rare diseases. The latter two key leadership positions remain unfilled. . . .”
- The explanation of CFO Lorence Kim is less than reassuring from the standpoint of product safety and reliability: “ . . . . ‘We force everyone to grow with the company at unprecedented speed,’ Moderna Chief Financial Officer Lorence Kim said. ‘Some people grow with the company; others don’t.’ . . .”
- Beginning in 2013, Moderna partnered with a series of pharmaceutical giants, including AstraZeneca, which has been selected to develop a Covid-19 vaccine: “ . . . . That’s when Moderna — which had just 25 employees — signed a staggering $240 million partnership with UK pharmaceutical giant AstraZeneca. It was the most money pharma had ever spent on drugs that had not yet been tested in humans. . . .”
- The firm has been lavishly capitalized: “ . . . . In early 2015, Moderna disclosed a $450 million financing round, the largest ever for a private biotech company. This month, the company broke its own record, raising another $474 million. . . . Though it has yet to reveal data from a single clinical trial, Moderna is now valued at $4.7 billion, according to Pitchbook. . . .”
- Initially, Moderna aimed at developing products that would be administered for a period of years: “ . . . . From the start, Moderna heralded its ability to produce proteins within cells, which could open up a world of therapeutic targets unreachable by conventional drugs. The most revolutionary treatments, which could challenge the multibillion-dollar market for protein therapy, would involve repeated doses of mRNA over many years, so a patient’s body continued to produce proteins to keep disease at bay. . . .”
- Instead of producing treatments that would be administered over a period of years, the company focused on vaccines: “ . . . . But Moderna’s first human trials aren’t so ambitious, focusing instead on the crowded field of vaccines, where the company has only been working since 2014. . . . The choice to prioritize vaccines came as a disappointment to many in the company, according to a former manager. The plan had been to radically disrupt the biotech industry, the manager said, so ‘why would you start with a clinical program that has very limited upside and lots of competition?’” . . . .”
- The answer to Moderna’s focus on vaccines may be due to issues of product safety: “ . . . Delivery — actually getting RNA into cells — has long bedeviled the whole field. On their own, RNA molecules have a hard time reaching their targets. They work better if they’re wrapped up in a delivery mechanism, such as nanoparticles made of lipids. But those nanoparticles can lead to dangerous side effects, especially if a patient has to take repeated doses over months or years. . . .”
- Vaccines will only administer mRNA at the time of vaccination, rather than over a long period of time: “ . . . . ‘I would say that mRNA is better suited for diseases where treatment for short duration is sufficiently curative, so the toxicities caused by delivery materials are less likely to occur,’ said Katalin Karikó, a pioneer in the field who serves as a vice president at BioNTech. . . That makes vaccines the lowest hanging fruit in mRNA, said Franz-Werner Haas, CureVac’s chief corporate officer. ‘From our point of view, it’s obvious why [Moderna] started there,’ he said.’ . . .”
- Moderna’s explanation for its focus on vaccines is not reassuring—the speed with which it can proceed to human trials. The firm’s secrecy has generated alarm: “ . . . . Moderna said it prioritized vaccines because they presented the fastest path to human trials, not because of setbacks with other projects. ‘The notion that [Moderna] ran into difficulties isn’t borne in reality,’ said [chairman of the board Noubar] Afeyan. But this is where Moderna’s secrecy comes into play: Until there’s published data, only the company and its partners know what the data show. Everyone outside is left guessing — and, in some cases, worrying that Moderna won’t live up to its hype. . . .”
- Moderna applies software and a business model derived from Tesla, Amazon and Uber: “ . . . . Moderna has pioneered an automated system modeled on the software Tesla uses to manage orders, Bancel said: Scientists simply enter the protein they want a cell to express, and testable mRNA arrives within weeks. . . . That has always been part of the plan, former employees said, pointing to Bancel’s fascination with the tech industry. Uber and Amazon were not the first to come up with their respective business ideas, but they were the ones that built enough scale to ward off competition. And Moderna is positioning itself to do the same in mRNA. . . .”
At first glance, Moderna Therapeutics looks like the most enviable biotech startup in the world. It has smashed fundraising records and teamed up with pharmaceutical giants as it pursues a radical plan to revolutionize medicine by transforming human cells into drug factories.
But the reality is more complicated.
A STAT investigation found that the company’s caustic work environment has for years driven away top talent and that behind its obsession with secrecy, there are signs Moderna has run into roadblocks with its most ambitious projects.
At the center of it all is Stéphane Bancel, a first-time biotech CEO with an unwavering belief that Moderna’s science will work — and that employees who don’t “live the mission” have no place in the company. Confident and intense, Bancel told STAT that Moderna’s science is on track and, when it is finally made public, that it will meet the brash goal he himself has set: The new drugs will change the world.
But interviews with more than 20 current and former employees and associates suggest Bancel has hampered progress at Moderna because of his ego, his need to assert control and his impatience with the setbacks that are an inevitable part of science. Moderna is worth more than any other private biotech in the US, and former employees said they felt that Bancel prized the company’s ever-increasing valuation, now approaching $5 billion, over its science.
As he pursued a complex and risky strategy for drug development, Bancel built a culture of recrimination at Moderna, former employees said. Failed experiments have been met with reprimands and even on-the-spot firings. They recalled abusive emails, dressings down at company meetings, exceedingly long hours, and unexplained terminations.
At least a dozen highly placed executives have quit in the past four years, including heads of finance, technology, manufacturing, and science. In just the past 12 months, respected leaders of Moderna’s cancer and rare disease programs both resigned, even though the company’s remarkable fundraising had put ample resources at their disposal. Each had been at the company less than 18 months, and the positions have yet to be filled.
Lower-ranking employees, meanwhile, said they’ve been disappointed and confused by Moderna’s pivot to less ambitious — and less transformative — treatments. Moderna has pushed off projects meant to upend the drug industry to focus first on the less daunting (and most likely, far less lucrative) field of vaccines — though it is years behind competitors in that arena.
The company has published no data supporting its vaunted technology, and it’s so secretive that some job candidates have to sign nondisclosure agreements before they come in to interview. Outside venture capitalists said Moderna has so many investors clamoring to get in that it can afford to turn away any who ask too many questions. Some small players have been given only a peek at Moderna’s data before committing millions to the company, according to people familiar with the matter.
“It’s a case of the emperor’s new clothes,” said a former Moderna scientist. “They’re running an investment firm, and then hopefully it also develops a drug that’s successful.”
Like many employees and former employees, the scientist requested anonymity because of a nondisclosure agreement. Others would not permit their names to be published out of fear that speaking candidly about big players in the industry would hurt their job prospects down the road.
Moderna just moved its first two potential treatments — both vaccines — into human trials. In keeping with the culture of secrecy, though, executives won’t say which diseases the vaccines target, and they have not listed the studies on the public federal registry, ClinicalTrials.gov. Listing is optional for Phase 1 trials, which are meant to determine if a drug is safe, but most companies voluntarily disclose their work.
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An ambitious CEO dreams big
Bancel, 44, had no experience running a drug development operation when one of biotech’s most successful venture capitalists tapped him to lead Moderna. He’d spent most of his career in sales and operations, not science.
But he had made no secret of his ambition.
A native of France, Bancel earned a master’s in chemical engineering from the University of Minnesota and an MBA from Harvard in 2000. As Harvard Business School classmates rushed to cash in on the dot-com boom, Bancel laid out a plan to play “chess, not checkers.”
“I was always thinking, one day, somebody will have to make a decision about me getting a CEO job,” he told an audience at his alma mater in April. “… How do I make sure I’m not the bridesmaid? How do I make sure that I’m not always the person who’s almost selected but doesn’t get the role?”
He went into sales and rose through the operational ranks at pharmaceutical giant Eli Lilly, eventually leading the company’s Belgian operation. And in 2007, at just 34, he achieved his goal, stepping in as CEO of the French diagnostics firm bioMérieux, which employs roughly 6,000 people.
The company improved its margins under Bancel’s tenure, and he developed a reputation as a stern manager who got results, according to an equities analyst who covered bioMérieux at the time.
“He doesn’t suffer fools lightly,” the analyst said, speaking on condition of anonymity to comply with company policy. “I think if you’re underperforming, you’ll probably find yourself looking for another job.”
Bancel’s rise caught the eye of the biotech investment firm Flagship Ventures, based here in Cambridge. Flagship CEO Noubar Afeyan repeatedly tried to entice him to take over one of the firm’s many startups, Bancel said. But he rejected one prospect after another because the startups seemed too narrow in scope.
Moderna was different.
The company’s core idea was seductively simple: cut out the middleman in biotech.
For decades, companies have endeavored to craft better and better protein therapies, leading to new treatments for cancer, autoimmune disorders, and rare diseases. Such therapies are costly to produce and have many limitations, but they’ve given rise to a multibillion-dollar industry. The anti-inflammatory Humira, the world’s top drug at $14 billion in sales a year, is a shining example of protein therapy.
Moderna’s technology promised to subvert the whole field, creating therapeutic proteins inside the body instead of in manufacturing plants. The key: harnessing messenger RNA, or mRNA.
In nature, mRNA molecules function like recipe books, directing cellular machinery to make specific proteins. Moderna believes it can play that system to its advantage by using synthetic mRNA to compel cells to produce whichever proteins it chooses. In effect, the mRNA would turn cells into tiny drug factories.
It’s highly risky. Big pharma companies had tried similar work and abandoned it because it’s exceedingly hard to get RNA into cells without triggering nasty side effects. But if Moderna can get it to work, the process could be used to treat scores of diseases, including cancers and rare diseases that can be death sentences for children.
…
Under Bancel, Moderna has been loath to publish its work in Science or Nature, but enthusiastic to herald its potential on CNBC and CNN, taking part in segments on the world’s most disruptive companies and the potential “cure for cancer.”
…
Resignations, dismissals, and churn
From the beginning, Bancel made clear that Moderna’s science simply had to work. And that anyone who couldn’t make it work didn’t belong.
The early Moderna was a chaotic, unpredictable workplace, according to former employees. One recalls finding himself out of a job when a quick-turnaround experiment failed to pan out. Another helped train a group of new hires only to realize they were his replacements.
“There was a kind of Jack Welch-ian, ‘We fire the bottom 10 percent’ from the very beginning,” said a former Moderna manager. “That’s probably the biggest HR difference between Moderna and virtually any other biotech, where they talk so much about developing their people.”
Moderna went through two heads of chemistry in a single year, according to former employees, and its chief scientific officer and head of manufacturing left shortly thereafter. Those who fell out of favor with Bancel would find themselves excluded from key meetings, pushed aside until they resigned or ultimately got dismissed, employees said.
Most stunning to employees was the abrupt departure of Joseph Bolen, who came aboard in 2013 to lead Moderna’s R&D efforts.
Bolen was a big-name hire in biotech circles, an experienced chief scientific officer who had guided Millennium Pharmaceuticals to FDA approval for a blockbuster cancer drug. He’d been profiled in The Scientist, which dubbed him “the people’s CSO” for his ability to keep morale high and research focused. Landing him was a coup.
But two years into his tenure at Moderna, he abruptly stepped down last October, making no public statement save for changing his LinkedIn status to “resigned.”
“No scientist in his right mind would leave that job unless there was something wrong with the science or the personnel,” said a person close to the company at the time.
Insiders said Bancel had effectively pushed Bolen out, hiring parallel executives until Bolen was in charge of just “a postage stamp” worth of territory, as one former Moderna manager put it. Bolen declined to comment.
For his part, Bancel acknowledged the changes that limited Bolen’s power but insisted the parting was friendly. Bancel said he tried to convince Bolen to stay, but the scientist “voted himself off the island.”
Bolen wasn’t alone. Chief Information Officer John Reynders joined in 2013 to make Moderna what he called the world’s “first fully digital biotech,” only to step down a year later. Michael Morin, brought in to lead Moderna’s scientific efforts in cancer in 2014, lasted less than 18 months. As did Greg Licholai, hired in 2015 to direct the company’s projects in rare diseases. The latter two key leadership positions remain unfilled.
“You wonder,” influential biotech blogger Derek Lowe wrote last year, “if Moderna really is a rocket ship getting ready to launch and spray a formation of new drugs across the sky, then why are these people leaving?”
The company has a simple explanation: Moderna lives in dog years compared with other biotechs.
“We force everyone to grow with the company at unprecedented speed,” Moderna Chief Financial Officer Lorence Kim said. “Some people grow with the company; others don’t.”
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A gold rush for Moderna
Hoge, who joined the company in 2012, describes the early days of Moderna as “when we were living in the caves.” The company often had only enough cash to keep the lights on for six months at a time, he said. “The strategy was just to survive.”
Moderna 1.0, and life in the caves, came to a close in 2013, according to company lore.
That’s when Moderna — which had just 25 employees — signed a staggering $240 million partnership with UK pharmaceutical giant AstraZeneca. It was the most money pharma had ever spent on drugs that had not yet been tested in humans.
The agreement is commemorated in one of Moderna’s offices by a framed clipping from the New York Times. Page B7 of the March 21, 2013 edition: “AstraZeneca Makes a Bet On an Untested Technique.”
For AstraZeneca, the unprecedented deal came at a time of uncertainty. A series of clinical failures had led the firm to fire its head of research and lay off 1,600 scientists. Pascal Soriot, just six months into his tenure as CEO, was under pressure from investors to chart a new course. And Moderna, with its brash ambition to bring 100 drugs to clinical trials within a decade, gave Soriot a way forward.
The rich deal started a gold rush for Moderna. Everyone, it seemed, wanted in.
Before the end of 2013, Moderna would turn heads again with a $110 million investment round, followed by a high-dollar partnership with biotech giant Alexion.
In early 2015, Moderna disclosed a $450 million financing round, the largest ever for a private biotech company. This month, the company broke its own record, raising another $474 million.
The run-up was “biotech fervor to the extreme,” according to a venture capitalist not involved with the company, requesting anonymity to speak candidly. While bigger investors got to see all the company’s data from animal experiments, some of Moderna’s smaller investors put in funds based on just a peek, according to people familiar with the process. Moderna’s fundraising success had created a seller’s market: Why deal with the questions of one potential investor when it had 10 more lined up?
Afeyan, Moderna’s chairman and cofounder, insists the company’s investors have done their homework. To say they bought in without due diligence “would be a bit of an insult to these people,” he said.
Though it has yet to reveal data from a single clinical trial, Moderna is now valued at $4.7 billion, according to Pitchbook.
That’s twice as much as Spark Therapeutics, the company widely expected to market the United States’s first gene therapy, which has shown signs in clinical trials that it can reverse blindness caused by a rare genetic disorder. Moderna is also worth billions more than Juno Therapeutics and Kite Pharma, startups developing novel treatments for cancer that have demonstrated promising results in early human trials.
Moderna has long shaken off rumors that it is soon to market its shares on Wall Street, with Hoge likening the company to a child star: “You don’t want to go through your adolescence publicly,” he told STAT.
But that’s about to change. Moderna’s next planned step is an initial public offering, according to a person close to the company. Bancel declined to say just when Moderna might go public, but the company has already prepared: In its latest filings with the Securities and Exchange Commission, Moderna changed its business structure from an LLC to a C corporation, completing a necessary step before mounting an IPO.
A strategic shift to less ambitious targets
With a public listing come required disclosures, and many are eager to see what Moderna’s been keeping under wraps all these years.
Outsiders and competitors, looking only at Moderna’s public statements, have noted a shift in strategy that might signal undisclosed setbacks.
From the start, Moderna heralded its ability to produce proteins within cells, which could open up a world of therapeutic targets unreachable by conventional drugs. The most revolutionary treatments, which could challenge the multibillion-dollar market for protein therapy, would involve repeated doses of mRNA over many years, so a patient’s body continued to produce proteins to keep disease at bay.
But Moderna’s first human trials aren’t so ambitious, focusing instead on the crowded field of vaccines, where the company has only been working since 2014.
First are the two vaccine trials for undisclosed infectious diseases. Coming next is a one-time treatment for heart failure, developed in partnership with AstraZeneca, followed by another experimental vaccine, for Zika virus, which several other pharma companies are also working to develop. And after that, Moderna is planning a human trial of a personalized cancer vaccine using mRNA, something it just came up with last year.
The choice to prioritize vaccines came as a disappointment to many in the company, according to a former manager. The plan had been to radically disrupt the biotech industry, the manager said, so “why would you start with a clinical program that has very limited upside and lots of competition?”
The answer could be the challenge of ensuring drug safety, outsiders said.
Delivery — actually getting RNA into cells — has long bedeviled the whole field. On their own, RNA molecules have a hard time reaching their targets. They work better if they’re wrapped up in a delivery mechanism, such as nanoparticles made of lipids. But those nanoparticles can lead to dangerous side effects, especially if a patient has to take repeated doses over months or years.
Novartis abandoned the related realm of RNA interference over concerns about toxicity, as did Merck and Roche.
Moderna’s most advanced competitors, CureVac and BioNTech, have acknowledged the same challenge with mRNA. Each is principally focused on vaccines for infectious disease and cancer, which the companies believe can be attacked with just a few doses of mRNA. And each has already tested its technology on hundreds of patients.
“I would say that mRNA is better suited for diseases where treatment for short duration is sufficiently curative, so the toxicities caused by delivery materials are less likely to occur,” said Katalin Karikó, a pioneer in the field who serves as a vice president at BioNTech.
That makes vaccines the lowest hanging fruit in mRNA, said Franz-Werner Haas, CureVac’s chief corporate officer. “From our point of view, it’s obvious why [Moderna] started there,” he said.
Moderna said it prioritized vaccines because they presented the fastest path to human trials, not because of setbacks with other projects. “The notion that [Moderna] ran into difficulties isn’t borne in reality,” said Afeyan.
But this is where Moderna’s secrecy comes into play: Until there’s published data, only the company and its partners know what the data show. Everyone outside is left guessing — and, in some cases, worrying that Moderna won’t live up to its hype.
“Frankly, I hope that there’s real substance and I hope they solve those challenges, because it’s not going to be good for the broader biotech industry in general if this thing implodes,” said one investor not involved with Moderna.
And it could still go either way, former employees said. If Moderna’s promises come to fruition, it could be a pillar of the biotech industry. If they don’t, it could find a place among a short list of companies that have cast a shadow over the entire industry and left investors disillusioned.
“Either we’ll be talking about it as the next Genentech,” a former Moderna manager said, “or we’ll think, ‘Well, back then, first there was Turing, then there was Valeant, and then there was Moderna.”
Enough cash to absorb some setbacks
Moderna’s management and its investors are keeping the faith, pointing to the company’s pipeline of 11 drug candidates and more than 90 preclinical projects.
And with Moderna’s huge cash reserves — estimated at $1.5 billion — it can afford a few setbacks, proponents said. The company said it’s pouring money into its manufacturing operation, planning to spend $100 million this year on a new plant. Moderna has pioneered an automated system modeled on the software Tesla uses to manage orders, Bancel said: Scientists simply enter the protein they want a cell to express, and testable mRNA arrives within weeks.
“If we have a bump in the road in the clinic, we will not have to wait years to go back to the drawing board,” Bancel said.
That has always been part of the plan, former employees said, pointing to Bancel’s fascination with the tech industry. Uber and Amazon were not the first to come up with their respective business ideas, but they were the ones that built enough scale to ward off competition. And Moderna is positioning itself to do the same in mRNA.
“Now, as we’re going to human [trials], it’s pretty clear no one else is going to catch us,” said Dr. Kenneth Chien, a professor at Karolinska Institutet working with Moderna and AstraZeneca.
Dr. Tal Zaks, Moderna’s chief medical officer, promises that the company will soon break its silence on the publishing front. He said next year Moderna will disclose the animal data that helped get its two vaccines into the clinic. The company has also committed to publishing full results from all of its human trials, starting with the vaccine studies next year.
Moderna’s reticence to share data earlier is “not because we decided to be secret,” Zaks said. “This is the natural evolution of a platform. As we go into the clinic, we will be very transparent.”
4. Moncef Slaoui’s optimistic statement on the Friday before the Monday announcement, presents important context for Moderna’s Monday announcement. That announcement moved markets based on inadequate data. “Operation Warp Speed” (headed by Slaoui) suggests that candidate Trump is very interested in those preliminary results as well.
” . . . . Following Moncef Slaoui’s Friday appointment as a co-leader of the Warp Speed program, he’s set to sell about 155,000 shares in Moderna, according to press reports. They were worth an estimated $10 million Friday, but after Monday’s stock run-up on positive early data, they’re now valued at about $12.4 million. . . . Following Slaoui’s selection, Sen. Elizabeth Warren tweeted that it’s a ‘huge conflict of interest’ for him to keep the Moderna stock as he assumes the new role. She said he should ‘divest immediately.’ In a now-deleted tweet, Slaoui responded that there ‘is no conflict of interest, and there never has been,’ Business Insider reports. . . .”
As the Operation Warp Speed program races ahead with COVID-19 vaccine candidates, one of its new leaders kept millions of dollars of stock in Moderna, the biotech leading the pack.
But now, after an influential senator challenged that ownership interest, he’s planning to sell.
Following Moncef Slaoui’s Friday appointment as a co-leader of the Warp Speed program, he’s set to sell about 155,000 shares in Moderna, according to press reports. They were worth an estimated $10 million Friday, but after Monday’s stock run-up on positive early data, they’re now valued at about $12.4 million.
Slaoui is set to donate to cancer research the excess proceeds from the sale, or about $2.4 million, according to CNBC. Slaoui also resigned as a Moderna board member with the appointment.
President Donald Trump unveiled the “Warp Speed” project at a Rose Garden event on Friday. Aside from Slaoui, a GlaxoSmithKline veteran, the four-star general Gustave Perna will also lead the program.
Following Slaoui’s selection, Sen. Elizabeth Warren tweeted that it’s a “huge conflict of interest” for him to keep the Moderna stock as he assumes the new role. She said he should “divest immediately.”
In a now-deleted tweet, Slaoui responded that there “is no conflict of interest, and there never has been,” Business Insider reports.
Slaoui spent nearly three decades at GlaxoSmithKline and retired in 2017. Then, he joined the boards of Moderna and other life sciences companies.
Operation Warp Speed is aiming to deliver a COVID-19 vaccine by the end of the year. At Friday’s event, Slaoui said he was “confident” in that goal after viewing early data from an undisclosed program. Moderna announced its promising data, from eight patients in a phase 1 study, early Monday morning. . . .
5. Even after agreeing to sell his Moderna stock, Slaoui’s investments raise alarming questions–note that he is a “venture capitalist” and a longtime former executive at Glaxo-Smithkline:
- The circumstances of his appointment will permit him to avoid scrutiny: ” . . . . In agreeing to accept the position, Dr. Slaoui did not come on board as a government employee. Instead, he is on a contract, receiving $1 for his service. That leaves him exempt from federal disclosure rules that would require him to list his outside positions, stock holdings and other potential conflicts. And the contract position is not subject to the same conflict-of-interest laws and regulations that executive branch employees must follow. . . .”
- He will retain a great deal of Glaxo-Smithkline stock: ” . . . . He did not say how much his GSK shares were worth. When he left the company in 2017, he held about [500,000 in Western Print Edition] 240,000 shares and share equivalents, according to the drug company’s annual report and an analysis by the executive compensation firm Equilar. . . .”
- Further analysis of Slaoui’s position deepens concern about the integrity of the process: ” . . . . ‘This is basically absurd,’ said Virginia Canter, who is chief ethics counsel for Citizens for Responsibility and Ethics in Washington. ‘It allows for no public scrutiny of his conflicts of interest.’ Ms. Canter also said federal law barred government contractors from supervising government employees. . . . Ms. Canter, a former ethics lawyer in the Obama and Clinton administrations, the Securities and Exchange Commission and other agencies, pointed out that GSK’s vaccine candidate with Sanofi could wind up competing with other manufacturers vying for government approval and support. ‘If he retains stock in companies that are investing in the development of a vaccine, and he’s involved in overseeing this process to select the safest vaccine to combat Covid-19, regardless of how wonderful a person he is, we can’t be confident of the integrity of any process in which he is involved,’ Ms. Canter said.In addition, his affiliation with Medicxi could complicate matters: Two of its investors are GSK and a division of Johnson & Johnson, which is also developing a potential vaccine. . . .”
. . . . The scientist, Mocef Slaoui, is a venture capitalist and a former longtime executive at Glaxo-Smithkline . . .
. . . . In agreeing to accept the position, Dr. Slaoui did not come on board as a government employee. Instead, he is on a contract, receiving $1 for his service. That leaves him exempt from federal disclosure rules that would require him to list his outside positions, stock holdings and other potential conflicts. And the contract position is not subject to the same conflict-of-interest laws and regulations that executive branch employees must follow. . . .
. . . . He did not say how much his GSK shares were worth. When he left the company in 2017, he held about [500,000 in Western Edition] 240,000 shares and share equivalents, according to the drug company’s annual report and an analysis by the executive compensation firm Equilar.
He said he told administration officials that he did not want to sell his company stock.
‘I have worked for 29 years for GSK,’ Dr. Slaoui said. ‘I have never sold a single share of any company in my life. This is my retirement. What I said regarding the GSK shares, I said I cannot take the job if I have to sell them.’ . . .
. . . . Without public disclosure, some ethics experts called his contract an end-run around the rules.
“This is basically absurd,” said Virginia Canter, who is chief ethics counsel for Citizens for Responsibility and Ethics in Washington. “It allows for no public scrutiny of his conflicts of interest.”
Ms. Canter also said federal law barred government contractors from supervising government employees. . . .
. . . . Ms. Canter, a former ethics lawyer in the Obama and Clinton administrations, the Securities and Exchange Commission and other agencies, pointed out that GSK’s vaccine candidate with Sanofi could wind up competing with other manufacturers vying for government approval and support.
“If he retains stock in companies that are investing in the development of a vaccine, and he’s involved in overseeing this process to select the safest vaccine to combat Covid-19, regardless of how wonderful a person he is, we can’t be confident of the integrity of any process in which he is involved,” Ms. Canter said.
In addition, his affiliation with Medicxi could complicate matters: Two of its investors are GSK and a division of Johnson & Johnson, which is also developing a potential vaccine. . . .
6. Moderna stands to make billions of dollars if their vaccine goes to market:
- ” . . . . What investors are betting on, for Moderna and others developing vaccines against the SARS-CoV‑2 virus, is that a third of the developed world’s population will get vaccinated every year. That could amount to a $10 billion annual business, at an estimated price of $30 per vaccination. . . .”
- ” . . . . Morgan Stanley analysts this past weekend suggested that pricing might start at $5 to $10 a dose during this first pandemic crisis, then rise to a range of $13 to $30 for preventive doses in future years. But at BMO Capital Markets, analyst George Farmer speculated that Moderna could start charging $125 per treatment in the U.S. market and raise that price over time to $200. . . . ”
Fresh on the heels of the first data from human tests of its Covid-19 vaccine, Moderna sold $1.3 billion worth of stock on Monday at a price of $76 a share. That’s a fourfold rise from price where the biotech’s stock started the year, and a market value of $30 billion for a company that has yet to sell its first product.
What investors are betting on, for Moderna and others developing vaccines against the SARS-CoV‑2 virus, is that a third of the developed world’s population will get vaccinated every year. That could amount to a $10 billion annual business, at an estimated price of $30 per vaccination. At higher prices, Covid vaccine revenue would be bigger still.
In Tuesday morning trading, Moderna stock was down 5% from Monday’s close, at $76.
On a Monday conference call, Moderna CEO Stéphane Bancel said the Cambridge, Mass., company had not yet decided on a price , in the event that their mRNA-1273 vaccine proves effective in the Phase 2 and 3 trials it will run this year. He said that Moderna was thinking about what Covid-19 illness costs the health-care system.
Covid’s cost obviously goes beyond the hospital, and it’s already been gigantic . In the U.S. alone, nearly 90,000 have died in a few months’ time. The scale of the coronavirus’ impact explains why there’s such a range of estimates on Wall Street for what vaccine makers will charge. Morgan Stanley analysts this past weekend suggested that pricing might start at $5 to $10 a dose during this first pandemic crisis, then rise to a range of $13 to $30 for preventive doses in future years.
But at BMO Capital Markets, analyst George Farmer speculated that Moderna could start charging $125 per treatment in the U.S. market and raise that price over time to $200. Most of the world’s health-care systems are government-run, so Farmer’s model assumes that pricing abroad will be a fraction of America’s generous pricing.
Vaccinations will likely consist of a first shot and then a booster one month later. After clinical trials answer the first crucial question of whether vaccine candidates like Moderna’s prevent Covid in humans, the next question will be how long immunity lasts. Assuming somewhat less mutability than is the case with the flu virus, researchers are guessing that people might need a SARS-CoV‑2 vaccination every few years. That’s how analysts like BMO’s Farmer arrive at a count of roughly a third of the population needing a vaccination per year.
The U.S. population could rise from about 330 million today to more than 360 million by the decade’s end, depending on a bunch of social and economic factors, such as future immigration levels. Different age groups will get vaccinated at differing rates—hopefully unimpeded by antivaccination sentiments. BMO estimates that will work out to about 30% of America’s head count getting vaccinated each year, or some 100 million treatments a year by the second half of this decade. Put a price from $30 to $130 on those numbers, and you get $3 billion to $13 billion in U.S. sales.
Global sales are harder to forecast, with prices and vaccination rates likely to vary widely throughout the developed and developing countries. BMO’s Farmer guesstimates that sales in the developed world will amount to half or two-thirds the dollar levels of the U.S. Poorer nations will only be able to chip in around 5%. Still, he sees Covid vaccines exceeding $30 billion in sales by the end of the decade. That market size emboldened him to raise his price target on Moderna stock to $112 from $83, after yesterday’s encouraging news on the first handful of patients in Moderna’s Phase 1 trial.
Even if Moderna’s vaccine becomes the first one available—perhaps this fall, for front-line workers—it won’t be the only one. Pfizer (PFE) and its partner BioNTech (BNTX) are also in the clinic with a vaccine that uses technology similar to Moderna’s. And other vaccine approaches are being tested by the likes of Johnson & Johnson (JNJ) and the vaccine market incumbents Sanofi (SNY) and GlaxoSmithKline (GSK). . . .
7. We close the discussion with a reminder of the extent to which federal funding drives the value of Moderna: ” . . . . ‘Instead of waiting for the data and then scaling up with manufacturing process … we can make as many doses as we can. We are doing both in parallel,’ he said. The company plans to hire up to 150 people to support the effort. Bancel said the company ‘couldn’t have done this’ without the funding commitment from the Biomedical Advanced Research and Development Authority, which is part of the Department of Health and Human Services. . . .”
Moderna’s stock was surging Friday after the biotech company announced it has received as much as $483 million in federal funding to accelerate development of a coronavirus vaccine.
Shares of the Cambridge, Massachusetts-based firm closed 15.4% higher to $46.85. During Friday’s session, the stock hit an intraday all-time high of $49.
Moderna CEO Stephane Bancel said Friday on CNBC’s “Squawk Box” that the funding is particularly critical in aiding manufacturing efforts.
“Instead of waiting for the data and then scaling up with manufacturing process … we can make as many doses as we can. We are doing both in parallel,” he said. The company plans to hire up to 150 people to support the effort.
Bancel said the company “couldn’t have done this” without the funding commitment from the Biomedical Advanced Research and Development Authority, which is part of the Department of Health and Human Services.
Moderna has partnered with the National Institutes of Health on development of its Covid-19 vaccine. Phase 1 human trials of the potential vaccine began in the Seattle area in mid-March.
The trial was launched in “record speed,” White House health advisor Dr. Anthony Fauci said at the time.
Bancel on Friday reiterated Moderna’s timeline for vaccine development. He said he hopes to have safety data from the phase 1 trial this spring, which could allow it to advance to the next stage in the second quarter of this year.
The phase 1 trial is being conducted with 45 people, while phase 2 would involve an expansion into “hundreds of healthy subjects,” Bancel said.
Development also needs to include a large effectiveness study involving thousands of people, Bancel said. Moderna hopes to start that phase in the fall, depending on results from all the preceding stages. . . .
Uncle Sam and Il Duce
There was some good news on the COVID vaccine hunt revealed on Friday. Of course, as we’ll see, it’s the kind of good news that could possibly be used in a very bad way. So what’s the good news? Well, Moderna just released preliminary data on Friday about some safety studies on its COVID-19 vaccine. The results were pretty positive but they’re positive safety results from studies on mice, so it’s not really clear the findings will translate to humans. And that’s where this good news could possibly be used for bad ends. Because as we’ll see, there are growing concerns that, as the November 2020 US election grows closer the tempting for the Trump administration to declare the discovery of a vaccine is only going to grow too. So the temptation to basically rush the safety testing on a vaccine will be enormous and its a temptation that’s going to be felt by Moderna and the rest of the pharmaceutical industry too.
And what about the human clinical trials that should be the ultimate arbiter of the safety of these vaccines? Well, those trials are underway too. And as we’ll see in the second article below, they’re still conducting the phase II clinical trials and phase III is going to be getting underway in July. But that’s part of what’s kind of alarming about the situation: the human clinical trials are already underway at the same time the animal safety trials have yet to be completed. That’s how rushed everything is with this pandemic. And the phase II trial is going to be following people for the next year so it’s not really possible for the human clinical trials to really run to completion before November. Side effects can take a while to manifest. So it’s not really possible for a human safety trials to be complete before November but it is possible for animal safety trials to be completed. It points to kind of nightmare situation where political pressure results in side-effects that take a while to manifest getting missed as decision-makers decide to give undo weight to the animal safety results and just hope for the best.
So what were the positive results from the animal trials in mice? Well, mice were given the vaccine in a range of doses, included doses expected to elicit sub-protective response. Recall how exploring the interaction of COVID-19 with sub-protective immune responses (so low levels of antibodies that can’t prevent the disease) is one of the key safety issues to test given the possibility of Antibody Dependent Enhancement (ADE), a phenomena where low levels of ineffective antibodies latch onto the virus and exacerbate an overactive immune response that leads to the deadliest symptoms likes cytokine-storms. This danger was seen with SARS and attempts to create a SARS vaccine so it’s a reasonable fear with SARS-CoV‑2. So finding that mice don’t appear to suffer from ADE is actually great news given on dangerous ADE could be, especially in the context of creating a vaccine. We could literally create a vaccine that protects those who get a strong immune response while endangering those with sub-protective responses. A kind of eugenic vaccine. So this should be good news, assuming this good news isn’t used in place of meaningful safety trials in humans:
“Prior studies on a vaccine for SARS — a close cousin to the new virus that causes COVID-19 — suggests vaccines against this type of virus might have the unintended effect of causing more severe disease when the vaccinated person is later exposed to the pathogen, especially in individuals who do not produce an adequately strong immune response.”
Unintended side effects that may future exposure worse. Yeah, that’s definitely something we don’t want to do. But at least with mice that doesn’t seem to happen:
Then again, it’s possible the study is incomplete and disorganized, as one scientist appeared to see it. It’s a reminder that this good news is actually preliminary tentative good news:
Ok, now here’s an update on Moderna’s clinical trials on humans. It sounds like the Phase III trial is going to be started in July. It’s going to involve 30,000 people. Alarmingly, those 30,000 people will all be receiving the exact same dosage, 100 micrograms, and that means the phase III trial won’t be testing sub-optimal dosages. It will implicitly be testing sub-protective immune responses since some of those 30,000 people will have sub-protective responses. But it doesn’t sound like the exploration of sub-protective dosages will be thoroughly explored using this large sample size. So we’re already learning that the big Phase III trial basically won’t be very interested in testing ADE in humans.
What about the Phase II trial? Well, that trial of 600 healthy people is ongoing. The volunteers will be followed for a year after their injections to examine the safety of the vaccine. The Phase II trial will also include people from key populations like health care workers and residents in long-term care facilities. So the Phase II trial is going to provide crucial safety information on the most vulnerable and important populations to watch out for with this vaccine but it won’t be completed for a year. All in all, it’s the perfect storm for having just enough safety information to make rushed vague education guesses and that’s about it:
“The trial will test just one dose level of the vaccine, 100 micrograms, given in two shots. In the earlier phase 1 study involving 45 healthy volunteers, the company explored lower and higher doses, but preliminary results revealed by the company from this trial suggested that 100 micrograms provided the desired immune response safely. According to the company, the vaccine produced antibodies against the COVID-19 virus in those who were vaccinated, and in tests involving a handful of participants, those antibodies were able to neutralize the virus in the lab. The full details of that study aren’t available yet; that will soon be published by Moderna’s collaborators, a team of scientists at the National Institute of Allergy and Infectious Diseases.”
So based on the Phase I trial of 45 healthy volunteers, 100 micrograms was determined to provide the desired immune response safely and that’s the dosage that’s going to be used on 30,000 volunteers for the Phase III trial. Let’s hope that Phase I trial’s sample size was adequate and representative of the population. Especially the unhealthy part of the population that’s going to be most vulnerable to side-effects.
And this Phase III trial is going to taking place at the same time Phase II is continuing. It sounds like it’s Phase II where key populations, like health care workers and long-term care facility residents are going to be examined. Specifically healthy volunteers. So healthy long-term care residents are being used as the test sample for the safety of this vaccine. And we’ll find out the results in a year. Hmmm...
Ok, finally, here’s a New York Times opinion piece by by Drs Ezekiel J. Emanuel and Paul A. Offit where they speculate bout the possibility of some sort of near-future dystopian sci-fi nightmare scenario playing out in the coming months. A near-future dystopian sci-fi nightmare scenario that seems all too plausible given the dystopian political nightmare reality of present-day America and its dystopian fascist president who is desperate for a big COVID ‘win’ ASAP:
“Given how this president has behaved, this incredibly dangerous scenario is not far-fetched. In a desperate search for a political boost, he could release a coronavirus vaccine before it had been thoroughly tested and shown to be safe and effective.”
That’s the generic scenario that seems all too plausible: In a desperate search for a political boost, Trump basically pressures the FDA into approving a vaccine before the election. A scenario the vaccine manufacturers show no inclination to resist. As they note, Moderna isn’t the only company talking about delivering a vaccine before fall. Astra Zeneca has been making those kinds of bold pledges too:
And note their warnings about the sample sizes needed to detect rare side-effects and the importance of finding those rare effects: Even if they’re rare and therefore don’t impact a huge portion of the populace, if we miss those rare effect and a bunch of people are harmed by these vaccines that’s only going to erode already fragile public confidence in vaccines in general and fuel the anti-vaxxer crowd:
And that’s all why this initial preliminary good news from Moderna’s animal studies on the COVID vaccine is potentially bad news: when one of the biggest dangers is the preemptive abuse of preliminary good news by Trump good news becomes potentially catastrophic news.
So overall, the good news is that Moderna’s COVID vaccine doesn’t appear to trigger ADE in lab rats with sub-protective immune responses. The bad news is that if this good news is used by Trump to push a premature release of the vaccine before the human clinical trials are completed it’s going to effectively turn everyone who gets the vaccine into a lab rat. It’s going to be a really, really, really large human clinical safety trial and everyone will be enrolled.
Moderna is launching its Phase III coronavirus vaccine trial today with 30,000 people. This is the trial that’s going to determine if the vaccine actually works in a meaningful way. If it works it will probably be approved for widespread use so the stakes are quite high. Especially since, as we’ve seen, this Phase III trial is taking place at the same time the Phase II safety trials are still ongoing along with animal safety experiments.
It’s that context that brings us to a STAT News article from last week that recommended to members of the House Energy and Commerce Oversight and Investigations Subcommittee six burning questions they should ask for coronavirus vaccine manufacturers during the committee hearing that took place last Tuesday.
Executives from a number of different companies racing to develop a SARS-CoV‑2 vaccine appeared before the committee to take questions about their plans to both develop a safe vaccine and massively scale up production to make it available to the public and there was one particular recommended question for the vaccine manufacturers that really stood out in part because it’s so rarely asked amidst this unprecedented vaccine race: so in 2005 the US passed a law that shields vaccine and drug developers from liability if a drug or vaccine developed in response to a health emergency causes injuries to the people who receive it. If that liability protection was not in place would these companies be pursuing this vaccine? And perhaps more importantly, since this is global pandemic that needs to be addressed at a global level to truly be fixed, will US vaccine manufacturers make the vaccines they develop available in countries that don’t offer them the same liability shield?
They’re the kinds of questions that indirectly ask a question vaccine and drug developers undoubtedly have asked themselves many times but would prefer not to answer in public: just how much are they relying on this liability shield when making cost/benefit analyses involving patient safety. Keep in mind that Health and Human Services secretary Alex Azar announced back in March that the pandemic qualified as the kind of public health emergency that waived liability for vaccine and drug developers so this 2005 rule is currently in effect.
And sure, the companies would obviously prefer it if there are no negative side-effects from their products. But how much do they really care if there are side-effects thanks to that liability shield? We’re talking about profit-maximizing entities, after all.
Plus, as we’ve already seen with Moderna’s hunt for an COVID mRNA vaccine, it’s not just a hunt for a vaccine that can stop the virus. It’s also a hunt to establish the safety of mRNA technology in humans for the first time ever. An entire industry of new medicine that rely on this mRNA therapeutic approach but it’s never actually been established that this is safe and, as we’ve seen, the pharmaceutical industry has been trying and failing to develop the technology without side-effects for years now. They just can’t avoid the side-effects thus far. So that makes this pandemic an incredible opportunity specifically for mRNA vaccine manufacturers to get that untested technology widely rolled out to the public while avoiding liability if there are unforeseen (or foreseen and ignored) negative side-effects. And that perversely could encourage the mRNA vaccine manufacturers to take even greater risks with the public’s safety because this is the kind of opportunity that could establish mRNA technology as a safe and effective platform that could be used for all sorts of other products but this precious liability shield fades away as soon as a viable competitor vaccine gets developed.
Unfortunately, it doesn’t sound like these questions were actually asked during the hearing so these questions remain urgent open burning questions:
“Some manufacturers are suggesting that there may be enough data to warrant emergency use authorizations as soon as October. If that happens, vaccines destined for use in potentially billions of people will be deployed after mere months of human testing.”
Emergency use authorizations for these vaccines could come as soon as October according to some of the vaccine manufacturers. Keep in mind that emergency use authorizations imply the safety studies won’t have been completed by that point. So the industry is clearly very keen on getting these vaccines into people ASAP. But it’s the large-scale use of the vaccine that could come later where many of the rarer side-effects would be expected to manifest and it’s at that point that the liability shield from the Public Readiness and Emergency Preparedness Act of 2005 becomes invaluable for these companies. So would these companies still be pursuing these vaccines without the liability protection? And what about countries without similar liability protections? Are they going to be blocked from receiving the vaccine unless they extend the protections? These are the kinds of questions that are going to become more and more important the closer we get to reaching a point where a vaccine has been approved for large-scale use:
But these are also the of course the kinds of questions that we wouldn’t really expect these companies to honestly answer anyway. That’s why, while it’s kind of sad that these questions didn’t actually get asked of the pharmaceutical executives during the congressional hearing last week, it’s not like they were going to give meaningful answers anyway. They’re really questions congress and the public should be asking itself. Especially before we all start injecting these vaccines.
It’s also worth keeping in mind another nightmarish scenario we could be lurching towards: polls show around a third of Americans won’t take the vaccine even when it’s developed, which to some extent reflects the deep anti-vaccine skepticism that pervades the US society, especially among right-wing voters who have been binging on Alex Jones-style far right conspiracy theories for the last decade (or, increasingly, just binging on mainstream conservative media that has now mainstreamed Alex Jones). Now imagine a situation where a vaccine does get rushed to the public and there are really are widespread side-effects. That experience is going to create the kind of anti-vaxxer sentiment and general distrust of science in this society that could last generations, especially if the manufacturers manage make a wild profit and escape liabilities at the same time. In other words, if Operation Warp Speed moves too fast and people get hurt while investors remain untouched it could end up warping the US public’s ability to trust public health experts — by translating legitimate concerns about the for-profit nature of the US’s economy into generic concerns about the safety of vaccines — with all sorts of consequences during future pandemics.
So that’s all something that’s going to be increasingly important to keep in mind as we get closer and closer to rolling out a vaccine: It’s generally assumed that pharmaceutical companies won’t knowingly release a product they don’t know is safe due to concerns about possible legal liabilities but those liabilities don’t exist in this case. Big gambles can be taken with massive upsides and minimal downsides. At least minimal downsides for the investors.
Now that President Trump has made sabotaging the US Postal System — as a justification for not deploying universal mail-in voting in response to the coronavirus pandemic — a key plank in his 2020 reelection platform, it’s worth noting how this scandal could potentially become intertwined with another major election-related story: the race to develop a coronavirus vaccine as soon as possible.
How could the sabotage of the US Postal System relate to the vaccine hunt? Well, imagine that a vaccine gets declared to be safe and effective by the US government before election day. Let’s say a few weeks before the election. And let’s say there are around 100 million doses available, which wouldn’t be enough for every American but could still potentially cover a large number of the most vulnerable people. How would a vaccine announcement impact the ongoing GOP demands that mail-in voting be restricted as much as possible? It’s the kind of question Democrats should probably be asking themselves right because we can be sure the Trump team has been asking themselves similar questions and it’s the Trump team, with its control over the Operation Warp Speed project, that will have the power to make such a vaccine readiness declaration. And that, of course, makes all of the concerns and criticisms over how Operation Warp Speed is being managed all the more concerning.
So with those growing concerns about the veracity of the Operation Warp Speed vaccine development process in mind, here’s another reminder that those concerns over Operation Warp Speed haven’t gone away. Critics are still pointing out that the group continues to lack transparency, including transparency over the results from the various vaccine clinical trials underway.
There’s also new concerns over the proposed pricing of the potential vaccines and whether or not the project is being turned into a Golden Goose for connected insiders. For example, we’re learning that AstraZeneca has already pledged to delivery 300 million doses to the US at a cost of around $4/dose. Moderna, on the other hand, has already received $1 billion in government funding and secured a contract with the US government to deliver 100 million doses for another $1.5 billion, bringing it to a cost of around $25/dose paid by US tax-payers, putting Moderna’s vaccine at the high end of the cost/dose for the vaccines that Operation Warp Speed is working on. Why the price difference, especially given that Moderna has already received over $1 billion from the US government to help develop its vaccine? Well, the head of Operation Warp Speed, Moncef Slaoui, didn’t address the specific concerns about Moderna but instead made general assurances that the public is getting a good deal no matter what as long as it gets a working vaccine. The fact that Slaoui was formerly the chairman of Moderna’s product development committee doesn’t exactly help with those pricing concerns.
But there’s one aspect of Moderna’s vaccine that makes its vaccine particularly important to keep an eye on in the context of this situation where a pre-election vaccine announcement could be used as an excuse to thwart mail-in voting: recall that part of what makes Moderna’s vaccine controversial is that it relies on mRNA delivery technology that hasn’t been approved for safe using in humans before. But there’s one massive advantage to mRNA vaccines over more traditional vaccine in that they are relatively cheap and easy to produce so rapid large-scale production of the mRNA vaccine is technologically conceivable. It’s the kind of situation that’s going to potentially make the Trump team even more keen on getting approval for Moderna’s vaccine as soon as possible. Because the sooner the Moderna vaccine is declared safe and ready to use, the sooner the Trump team can declare that actually mail-in voting isn’t needed anymore than anyone concerned about voting in the pandemic can just go and get the vaccine:
“Warp Speed’s upside — saving lives — is well worth any money that may get lost. But the program also has been shrouded in secrecy. The government has good reasons to keep some parts of the program under wraps, particularly negotiations that could affect the stock prices of companies making bids. But the process for deciding which companies were tapped to participate in the public health equivalent of the Manhattan Project has been entirely too opaque. And that lack of transparency is also likely to make the public — the folks who will have to line up for inoculations — skeptical that the government has ensured that we wind up with an effective, safe vaccine.”
As we can see, the early criticisms over Operation Warp Speed’s lack of transparency haven’t been resolved. It’s still opaque. Even to members of Congress apparently:
Then there are concerns that the companies selected to participate in Operation Warp Speed were selected not because they had the most scientifically promising approach but instead because they appeared to be able to manufacture a vaccine quickly. And when it comes to quick vaccine manufacturing it’s the mRNA-based vaccines like Moderna’s that lead the pack. The problem is mRNA vaccines haven’t actually been approved before:
And then there’s the fact that Moderna appears to be getting kind of a sweetheart deal in terms of the pricing of vaccine compared to the other vaccine developers. With a government contract of $1.5 billion for 100 million doses ($15/dose) on top of the $1 billion the government already gave to Moderna, that’s coming out to around $25/dose for those 100 million doses. And yet AstraZeneca — which is relying on a less risky technology for its vaccine — signed a deal that comes out to around $4/dose. Why the extra high price for a vaccine with unproven safety and massive government investments? Well, Slaoui — the former chairman of Moderna’s product development committee — gives us a general assurance that the deal could be worse compared to other hypothetical deals and if the US hadn’t created Operation Warp Speed it could have been forced to buy another country’s vaccine at a much higher price with limited supply. That was his answer to questions about why the US government is paying such a high price for a vaccine it paid to developed: that if the US didn’t do this it might end up paying an even higher price buying the vaccine from someone else:
And that’s how Moncef Slaoui answered questions posed to him about Operation Warp Speed: with non-answer deflections.
So as we get closer and closer to the election in the midst of this Post System sabotage scenario it’s going to be extra grimly interesting to watch how the various clinical trials involving Operation Warp Speed vaccines plays out, especially given the apparent lack of transparency even for health experts. If the Trump administration is going to use a vaccine announcement as an excuse to minimize mail-in voting that announcement is probably going to have to happen at least by early October.
Now here’s another story that reveals a new area of concern over the vaccine clinical trials. In particular Moderna’s big Phase III clinical trial that’s currently underway: despite the fact that over half othe patients hospitalized for the coronavirus in the US have been black and latino these groups only account for 15 percent of the clinical trial participants. Keep in mind that the black and latino population play a disproportionate role in the kinds of “essential” service jobs — like food services — that can’t be done remotely and instead puts them regular contact with the public and makes them the most likely to be exposed. That is precisely the demographic you want to use for your vaccine trial while widespread social-distancing is being deployed precisely because these front-line workers will almost certainly be exposed to the virus and are the most likely to get sick. As the following article notes, by systematically excluding from the clinical trials the very population that is most likely to get sick it’s possible the vaccine’s roll out will have to be delayed. Would the Trump administration allow for a delay in the vaccine rollout due to a lack of minorities in the clinical trial? Keep in mind that by disproportionately include whites in the clinical trial the vaccine is getting extra-safe testing in the white population. Might the administration instead approve the vaccine for whites only? Will we have a scenario where white people are told they can safely get the vaccine before the election while non-whites should abstain?:
“Black people represent 22% of coronavirus cases, but only 4.5% of Moderna’s study participants. Latinos represent 33% of cases, but only 10% of Moderna’s participants.”
As we can see, Moderna’s phase III clinical trials, which are supposed to be large scale enough to assess the safety and efficacy of the vaccine for final approval, aren’t large scale enough when it comes to blacks and Latinos. And that could, in theory, result in government agencies like the CDC telling Moderna they need to continue their trials. At least assuming the Trump administration allows such a delay to happen:
And then there’s the fact that by undersampling minority groups the clinical trials are effectively undersampling the part of the US populace that’s most likely to actually be exposed to the virus. So this is potentially screwing up the ability to meaningfully interpret the results of the clinical trials for all groups:
Is Moderna going to adequate find enough minority participants for its trial? Hopefully, but if not that’s going to potentially create a very awkward situation if the phase III results indicate the vaccine is safe and effective for use. It’s one of the many questions swirling around Operation Warp Speed as we get closer and closer to the election. Questions that now include whether or not the Trump administration is going to try to use a vaccine announcement as a reason to continue blocking mail-in voting. And questions of whether or not having a ‘approved-for-whites-only’ vaccine is exactly what the Trump administration prefers. At a minimum such a vaccine would be very on-brand for Trump’s reelection campaign.
Here’s an article about the ongoing clinical trials of Moderna’s COVID-19 vaccine and concerns over the inherent weaknesses in how those clinical trials were structured. First, recall the concerns over the significant lack of non-white participants in Moderna’s large-scale phase III clinical trial that recently got underway. Next, recall the intriguing finding that the T‑cells generated by exposure to common cold coronaviruses have demonstrated an ability to fight off SARS-CoV‑2 which is an exciting finding but also present a potential complication when assessing the effectiveness of vaccines because preexisting T‑cells may be a confounding factor in determining whether or not the vaccine triggers the production of T‑cells. Also recall the studies that found obesity appears to complicate the effectiveness of vaccines, a problem that could be particularly acute in the US but also in the elderly in general. Next, recall how the Phase III clinical trials are getting underway at the same time the Phase II trials — which are intended to assess longer-term safety concerns — aren’t going to be completed until next year. Finally, recall how when Moderna initially released early results from its Phase I trials — a release that happened to trigger a Moderna stock surge — touting how it discovered the vaccine triggered the production of neutralizing antibodies, it was data based on only 8 individuals in a trial of 45 people and all we were told about the demographics of those 8 people was that they were aged 18–55, leaving open the question of how effective the vaccine is in the elderly adults.
Well, Moderna just released more results from its Phase I clinical trial and this time it’s results for their elderly test set. Moderna characterizes the results as “promising”. Each person got two 100 microgram vaccine doses 28 days apart and all developed neutralizing antibodies and T‑cells. There were also no major side effects reported. Some reported fatigue, chills, headaches and pain at the injection site, but the majority of symptoms resolved within two days. Overall, that sounds like good news.
But of course there’s a catch: these results are based on 20 people in total. 10 individuals aged 56–70 were in one group and another 10 individuals aged 71 and older were in the second group. That’s it. From a statistical standpoint it’s not exactly a large sample that should lend confidence to the results, especially since the elderly is target population for this vaccine. Given the wild range of health complications the elderly experience it’s virtually impossible they could have explored all of the various subgroups (i.e. people suffering from obesity, diabetes, heart complications, etc). And given the difficulties Moderna has had in getting non-white participants for their Phase III trials we can also be pretty confident that this tiny the cohort probably wasn’t very demographically diverse, although no information on the race or the participants was released.
Now, in fairness to Moderna, they probably shouldn’t be testing their vaccine on large numbers of elderly in a Phase I trial since one of the main purposes of the Phase I trial is establishing safe parameters for conducting the larger Phase II and Phase III trials. So we can’t really blame Moderna for having a tiny sample size. The problems from the tiny sample size are instead related to the extremely rushed nature of this whole vaccine development process and the temptation to read too much into these statistically questionable results. For example, is the elderly cohort used for this tiny trial that found minimal side-effects going to be meaningfully representative of the safety of this vaccine for the much larger Phase III trials? Were the 10 people over the age of 70 relatively healthy individuals for their age? If so, are the much larger number participants over age 70 in the Phase III trial also just going to be relatively healthy too? Will patients with typical elderly comorbidities like obesity, heart disease or diabetes also going to be included in the Phase III trial? If so, we probably shouldn’t be surprised if there are a number of surprise side-effects for that group. And if not, then the Phase III trial won’t really be reflecting a true safety assessment for literally the target demographic for the vaccine. These are examples of the highly precarious nature of a rushed vaccine...especially when it involves mRNA technology that’s never been approved for use before.
So, overall, the news out of Moderna’s trial could be worse. They could have found that none of the participants generated antibodies and instead just got nasty side-effects but that’s now what they found. But thanks to the extremely tiny size of this cohort it’s still an open question as to whether or not these relatively positive results actually apply to the group of people who need the vaccine the most:
“Scientists had previously cautioned that the phase one study was small, and the results may differ for other populations, including the elderly who generally mount a weaker immune response. The new data Wednesday will likely boost hopes that there could be a safe and effective vaccine to prevent Covid-19 by the end of the year or early 2021.”
Yes, scientists had previously warned that the earlier Phase I results was too small and may not be representative of how the vaccine will react in other groups like the elderly. So now that Moderna has released relatively positive results from an extremely tiny cohort of the elderly hopes are up that a vaccine could be available by the end of the year despite the fact that a 10 person cohort of people over the age of 70 couldn’t possible be representative of the full range of people in that demographic, both from a race/ethnicity standpoint but also from a health complication standpoint. After all, when it comes to health complications you aren’t going to find a more diverse group than the elderly.
But, again, the results could be worse. They could have found no antibody or T‑cell production and lots of side-effects on this tiny cohort but that’s not what they found. The volunteers generated neutralizing antibodies and T‑cells. As the article notes, we just recently had the first confirmed case of someone catching COVID-19 again after recovery months earlier so the generation of those T‑cell is a crucial finding since T‑cells are what provide the longer-term immunity after the antibodies fade:
But that T‑cell finding raises the question: Are we sure these are T‑cells generated by the vaccine or might these be preexisting T‑cells that were already present from past exposure to common-cold coronaraviruses? At this point we don’t know because those details of the study aren’t yet publicly available.
And that’s all why these reports of possible good news from the vaccine trials are possible going to be bad news in the long run. These bits of good news would be great if these vaccines were being developed under a normal vaccine development schedule that takes years. But that’s not our circumstance. Instead, we’re going to be forced to essentially make educated guesses about the safety and efficacy of these vaccines based on incomplete or inadequate clinical trials.
There’s the old saying about product development: Good/Cheap/Fast. Pick two. But it’s going to be important to keep in mind that when it comes to rushed vaccine development, the “Good/Fast” option isn’t really available...unless it’s part of a “Good/Fast/Lucky” combo.
Oh look at that: it turns out Moderna didn’t disclose its billions of dollars in subsidies provided by the US government for developing a COVID-19 vaccine when the company applied for its vaccine patents. No mention at all. That was the finding of an NGO, Knowledge Ecology International, that examined over a dozen of Moderna’s patent applications related to the vaccine. The group is arguing that these federal subsidies should be disclosed not only due to basic transparency concerns but also because Moderna has yet to pledge to make a vaccine widely available for cheap.
The group cites one particular patent for a coronavirus vaccine that Moderna filed in February of this year call the “Betacoronavirus mRNA vaccine”. The vaccine appears to be based on the work Moderna had previously done on a Middle East respiratory syndrome (MERS) vaccine. As the following STAT News article notes, this patent cites two Moderna researchers as the inventors and while both of them mention in published academic papers that they were working under DARPA awards there’s no mention of this in the patent application.
Interestingly, the patent describes it as a vaccine for the entire family of known Betacoronaviruses like SARS-CoV (the original SARS), MERS, and the ‘common cold’ coronaviruses. But there’s no mention in the patent of the SARS-CoV‑2 virus that was already causing a pandemic at the time of the filing. So that’s pretty interesting: in February of this year Moderna filed for a patent for a generic Betacoronavirus vaccine and in the patent they suggest it could be used against all known Betacoronaviruses known infect humans, with no mentions of SARS-CoV‑2. Here’s the summary description from the patent application:
A text search of that patent filing reveals no instance of with “SARS-CoV‑2”, “COVID-19”, or “2019-nCoV” (the original name for the virus) and you will find no hits. So it sounds like this Betacoronavirus vaccine was proposed to work against a wide variety of Betacoronaviruses, and yet there was no mention of the Betacoronavirus that was already threatening the world by February of this year which raises the obvious question of what’s difference is between this vaccine and the vaccine Moderna is developing for SARS-CoV‑2. Is there a difference? The SARS-CoV‑2 vaccine is presumably based specifically on the SARS-CoV‑2 sequence so it seems likely the vaccine is is better tailored to this particular virus. Still, as we’ll also see, one of the reasons Moderna was allowed to fast track its SARS-CoV‑2 vaccine for clinical trials is because of the clinical trials it had already conducted on its MERS vaccine...clinical trials done in partnership with the National Institute of Allergy and Infectious Diseases (NIAID). It’s another example of the extensive government funding involved with the development of Moderna’s SARS-CoV‑2 vaccine. Extensive government funding Moderna just couldn’t bother to mention in its patent filing:
“In arguing for an investigation, the advocacy group maintained Moderna is obligated under federal law to disclose the grants that led to nearly a dozen specific patent applications and explained the financial support means the U.S. government would have certain rights over the patents. In other words, U.S. taxpayers would have an ownership stake in vaccines developed by the company.”
Did Modern violate federal law? That’s that these NGOs are arguing, along with the argument that the US government should own a stake in these vaccines. And when you put those two arguments together you can understand why Moderna would have been so interested in not mentioning this extensive government support. And it’s particularly notable in the patent from February of this year for a generic Betacoronavirus that lists two DARPA-funded Moderna researchers as the inventors:
But while Moderna may not have been open about its extensive government support in its patent filings, the company has been pretty open about it with the press. And for good reason: the fast-tracking of Moderna’s COVID-19 vaccine development has been justified in large part based on that extensive past government support, in particular the close work Moderna and US government agencies have conducted together over the years developing this vaccine technology for MERS:
“One of the reasons the SARS-CoV‑2 vaccine development has been so fast (for details, see the timeline of events at the bottom of the story) is the work Moderna has done over the past two years in an existing collaboration with the Vaccine Research Center (VRC) of NIAID to develop a vaccine against MERS-CoV.”
Yes, without all of the previous work on on developing a MERS vaccine the company wouldn’t have been capable of doing this fast-tracked development pipeline. Previous work done in collaboration with the Vaccine Research Center (VRC) of NIAID:
And that collaboration raises another question: so was it Moderna staff or their government collaborators at the NIAID who first developed this new COVID-19 vaccine earlier this year after the viral sequence was first release? Well, based on the following Nature article from last month describing the early race for a vaccine, it sounds like the existing collaboration between the NIAID’s Vaccine Research Center and Moderna that was on a different vaccine simply shifted gears and started working on the COVID-19 vaccine which means it’s been a US government/Moderna collaboration from the very beginning:
“Graham and his colleagues were just about to start manufacturing the Nipah vaccine for human trials when they got wind of a disease caused by a new coronavirus, now known as SARS-CoV‑2, wreaking havoc in Wuhan, China. They quickly changed their plans, but not the design on which their vaccine was based. Armed with the draft genome for SARS-CoV‑2, which was shared online on 11 January, Moderna swapped in the coronavirus RNA and started shipping a potential vaccine to the NIAID for clinical tests. The process took just six weeks — the fastest turnaround from project start to vaccine candidate in medical history.”
As we can see, it’s been a public-private partnership from the very beginning. A public-private partnership with exclusively private profits. At least that’s the stunt Moderna tried to pull with these patent applications. A stunt that just might succeed. We’ll see. DARPA has reportedly just opened an investigation of the patent filings today. Hopefully a fast-tracked investigation.
Here’s a set of disturbingly optimistic updates on the status of Operation Warp Speed and the US race for a COVID vaccine:
First, the Centers for Disease Control (CDC) sent a letter to all 50 states and 5 major cities to be prepared for the possibility of a vaccine distribution as early as late October or early November. The timing is obviously fueling the growing concerns of a rushed and politicized vaccine approval process, in part because they were sent on the same day of President Trump’s Thursday night Republican National Convention acceptance speech where he suggested that a vaccine might be available by the end of the year.
But as we’ll see in the second an third article excerpt below, those concerns are also heightened due to the recent comments from both the head of FDA, Stephen Hahn, and National Institute of Allergy and Infectious Diseases (NIAID) chief Dr. Anthony Fauci. Hahn just suggested that emergency authorization could be issue before the Phase III clinical trials, but just for certain groups, making it appear to be a kind of desperation-based reason for early vaccine approval. Fauci, on the other hand, described a far more optimistic scenario: that the independent advisory boards — which include members who are not part of the government and in theory wouldn’t be subject to the same pressures from the Trump administration as government employees — has to power to recommend the ending of clinical trials early and grant approval for the vaccine if the clinical trials show overwhelming efficacy. At that point, the vaccine developer would have to go to the FDA to request emergency authorization. So if the FDA does indeed issue emergency authorization before November it’s going to be crucial to find out of the independent advisory board recommended this or if it was a decision made unilaterally by the FDA.
But there’s another early vaccine release scenario that was just described by the last FDA chief, Scott Gottlieb, in an interview: one of the limiting factors in assessing the efficacy of a vaccine is the prevalence of the disease with vaccines for more prevalent and easily transmissible diseases being easier and faster to assess. So as Gottlieb pointed out, if the number of cases explodes so much in coming months that there’s a very large number of cases and the vaccine proves to be highly effective during this outbreak that could create the kind of epidemiological situation where we could feasible approve the vaccine before November.
So Trump can get his vaccine ‘October Surprise’ as long as the vaccine is shown to be highly effective in the midst of an explosion of new cases and all indications are that the federal government is trying to make that scenario happen. It’s a situation where there’s simultaneously incentives to exaggerate the safety of the vaccines while encouraging the spread of the virus. That’s why the CDC’s hyper-optimistic letter to the states is so ominous:
“Public health experts agree that agencies at all levels of government should urgently prepare for what will eventually be a vast, complex effort to vaccinate hundreds of millions of Americans. But the possibility of a rollout in late October or early November has also heightened concerns that the Trump administration is seeking to rush the distribution of a vaccine — or simply to hype that one is possible — before Election Day on Nov. 3.”
Anyone want an overhyped, rushed vaccine? Anyone? That’s the ironic challenge facing the Trump administration: if it rolls out the thing everyone wants too soon no one is going to want it.
And note that the “Vaccine A” and “Vaccine B” scenarios described in the CDC memo appear to match Pfizer’s and Moderna’s vaccines. And Pfizer has been indicating that it might be ready to seek government review for its vaccine as early as October. So the vaccine manufacturers appear to be happy to play along with any October Surprises:
Adding to potential concerns is that the CDC documents indicated that certain groups would be prioritized for early access to the vaccine. And some of those groups, like the elderly and minorities, are also the groups that many are concerned have been underrepresented in the ongoing clinical trials:
Next, here’s an interview of the head of the FDA, Stephen Hahn, about his willingness to fast-track a vaccine. The way Hahn puts it, the criteria for his decision to fast track is simply as long as the benefits outweigh the risks:
“In an interview with the Financial Times, Stephen Hahn said his agency was prepared to authorise a vaccine before Phase Three clinical trials were complete, as long as officials believed the benefits outweighed the risks. But he defended his embattled organisation against accusations that it was rushing the process to boost Mr Trump’s re-election prospects.”
Will the benefits of fast-tracked vaccine approval outweigh the risks? That’s going to be up to the FDA to decide and based on Dr. Hahn’s comments it sounds like he’s going to be quite open to the idea. It’s unclear to what extent Trump’s recent accusations of a “Deep State” plot at the FDA to slow down approvals is impacting Hahn’s decision-making, but the fact that Hahn and Trump jointly overhyped the value of convalescent plasma one day later doesn’t exactly lend confidence to Hahn’s ability to withstand Trump’s pressure:
Now here’s an interview Anthony Fauci just gave about what is probably the most optimistic scenario possible for ending the Phase III clinical trials early: if the early results are so positive there’s a perceived moral obligation to end the trial and make it available as soon as possible. If that happens, the independent advisory boards comprised of scientific experts — who hopefully aren’t subject to government pressures — can recommend ending the trial early, at which point it’s up to the vaccine developer to go to the FDA and request emergency authorization access.
Still, as critics point out, even if early results are overwhelmingly positive that doesn’t mean there aren’t dangerous side effects that can take longer to be detected. In addition, by ending the trial early that’s going to reduce the opportunity for recruiting more people from the groups that are currently under-represented in the trials like blacks and Hispanics. So it’s possible ending the trials early due to very positive early results could end up hiding very negative later results and end up obscuring complications that only show up in minority populations:
“The Data and Safety Monitoring Board could say, “‘The data is so good right now that you can say it’s safe and effective,’” Fauci said. In that case, researchers would have “a moral obligation” to end the trial early and make the active vaccine available to everyone in the study, including those who had been given placebos — and accelerate the process to give the vaccine to millions.”
If the best case scenario plays out and early results are amazing there’s nothing stopping the independent Data and Safety Monitoring Board from recommending an early end to the trial, although at that point it will still be up to the FDA to grant emergency authorization approval. This is why it’s going to be so important to determine whether or not the independent boards recommended any FDA emergency authorizations:
But even if the independent board does recommend ending the clinical trials early and authorizing emergency approval there’s still no way to truly assess the long-term risks of a vaccine. In addition, ending the trial early is only going to exacerbate existing short-comings in the trials like not having enough minority volunteers:
And finally, here’s an interview by Trump’s previous FDA chief, Scott Gottlieb, where he expresses skepticism that a vaccine could be ready before the November elections. It’s notable that Gottlieb sits on the board of Pfizer. But there is one scenario he saw as feasible for a pre-election vaccine release: if the clinical trials demonstrate that the vaccine is highly effective in the middle of a new “dense” wave of cases. In other words, Trump’s hope for a pre-election vaccine relies on an ongoin pre-election surge in cases because if you’re going to assess a vaccine in a short period of time the only way to do it is with a highly prevalent disease:
““I think it’s very unlikely. I think it’s more likely you’re going to get a top-line result some point in November and maybe be able to make a decision about an emergency use authorization after that,” the former Food and Drug Administration commissioner said on “Squawk Box.””
A pre-election vaccine announcement is very unlikely according to Gottlieb. But there’s one exception: the more effective the vaccine is the earlier that effectiveness will manifest itself in the clinical trials. So if the the vaccine is highly effective it’s possible that will because statistically apparent by October...if the pandemic also end up becoming “very dense” with a high transmission rate. Keep in mind that lower the transmission rate has been at the core of the efforts to prevent the spread of the virus:
And notice Gottlieb’s interpretation of Stephan Hahn’s comments about issuing pre-election emergency authorizations: Gottlieb wasn’t sure what Hahn was referring to but suggested that maybe certain groups, like front-line healthcare workers or the elderly and nursing home residents, might be granted emergency authorization. Don’t forget that it’s the elderly who are at most risk of any vaccine side-effects that aren’t detected in truncated clinical trials ended early:
A rushed vaccine authorized for just the elderly and nursing home patients. Is that going to be Trump’s October Surprise? If would be easier to dismiss the possibility if we hadn’t heard
all of these top official talking about the possibility of just that scenario this week. It would also be easier to dismiss if the Trump administration hadn’t just starting pushing a new “herd immunity” strategy this week. Yep, racing for “herd immunity” is back on the agenda of the White House thanks to, Scott Atlas, a new coronavirus adviser brought into the White House last month. And that “herd immunity” policy is precisely what could bring about the high transmission rates Gottlieb said would be required for early emergency authorization. So the good new related to all of this is that the vaccine is set to be very thoroughly tested thanks to the large number of cases in the US. That’s it. The rest is ominous news at best.
Here’s a troubling update on the AstraZeneca/OSI coronavirus vaccine safety trials that underscores how fundamentally difficult it can be to safely develop a vaccine: One of the volunteers experienced the kind of serious safety issue that, if seen again, could end the vaccine’s trial. The patient is suspected of experiencing something called transverse myelitis, which is an autoimmune response triggered by an antibody that causes the immune system to attack the body’s own tissue and can cause pain, muscle weakness, and paralysis and attack the spinal cord or brain. In this case the patient had an inflamed spinal cord. And while traverse myelitis may not be caused by the vaccine, the fear is that the vaccine induced a phenomenon called “molecular mimicry” where a piece of the vaccine is similar enough to tissue in the brain or spinal cord that it triggers the immune system to attack that tissue.
AstraZeneca is being criticized for the relative lack of information about the patient. It sounds like a volunteer in an earlier phase of the AstraZeneca trial also experienced a similar side effect, but it turns out she had multiple sclerosis that was unrelated to the vaccination which could have explained the phenomena. In the new case, AstraZeneca is refusing to release more information on the patient, citing patient privacy, although the company isn’t saying how disclosing more information would violate the their privacy. So the company itself is being disturbingly none forthright about this issue.
Keep in mind that the AstraZeneca vaccine isn’t based on the same experimental mRNA technology that Moderna’s and Pfizer’s vaccine use. Instead, it relies on a modified common cold virus. But that doesn’t mean there couldn’t be implications for these other vaccines. As the following article notes, one approach US vaccine researchers could take in light of this finding is to investigate the volunteers in the US-based trials for signs of inflammation in the spinal cord or brain, but it’s an investigation that could take one to two months. It’s an example of the many perils of a rushed vaccine. Perils that include possible autoimmune responses that attack the brain and spinal cord:
“The NIH has yet to get tissue or blood samples from the British patient, and its investigation is “in the planning stages,” Nath said. U.S. scientists could look at samples from other vaccinated patients to see whether any of the antibodies they generated in response to the coronavirus also attack brain or spinal cord tissue.”
An autoimmune response that attacks the brain and spinal cord. Yeah, that’s definitely one of the nightmare side-effects we’d like to avoid. So nightmarish that if another person ends up with transverse myelitis they’ll probably shut the trial down. And yet despite the potential severity of this finding AstraZeneca is remaining tight-lipped on any details:
Will we eventually get those patient details? We’ll see. But as the article notes, it’s still possible the vaccine will be released even knowing a small number of people might experience this side-effect possibly. There’s a balance of risks when you’re racing for a vaccine in the middle of a pandemic, after all:
And that willingness of the FDA to weigh the relative risks of not releasing a vaccine and potentially approve a vaccine despite these known risks is part of what this is significant update on the vaccine race. Because while a weighing of risks is certainly very appropriate and necessary, it’s hard to avoid the conclusion that if the FDA is forced to weigh those risks in, say, mid-October, those risks might include the risk of President Trump not getting re-elected without a vaccine announcement. It’s a timely reminder that if the FDA does indeed end up approving a vaccine “October Surprise”, that vaccine might contain a few surprises of its own. Surprises for the people receiving the vaccine, in this case. The FDA and AstraZeneca presumably wouldn’t be super surprised.
This September 23, 2020 Pro-Publica Article by Isaac Arnsdorf “Trump’s Vaccine Czar Refuses to Give Up Stock in Drug Company Involved in His Government Role” shows how far corruption by big pharma and the chemical cartel’s the Trump Administrations policies:
Portions of the Articles state:
The former pharmaceutical executive tapped by President Donald Trump to lead the administration’s race to a COVID-19 vaccine is refusing to give up investments that stand to benefit from his work — at least during his lifetime.
The executive, Moncef Slaoui, is the top scientist on Operation Warp Speed, the administration’s effort to develop a coronavirus vaccine in record time. Federal law requires government officials to disclose their personal finances and divest any holdings relating to their work, but Slaoui said he wouldn’t take the job under those conditions. So the administration said it’s treating him as a contractor. Contractors aren’t bound by the same ethics rules but also aren’t supposed to wield as much authority as full employees.
HHS previously said Slaoui “does not have any additional stock holdings in any other companies involved in vaccines, therapeutics and diagnostic products developed to combat COVID-19.” But in addition to Slaoui’s retained GlaxoSmithKline shares, the records obtained by the House Democrats revealed he has a holding in another biotechnology company, Lonza Group, that wasn’t previously disclosed. The company has a contract with Moderna to manufacture its coronavirus vaccine. Slaoui resigned from Lonza’s board before joining Operation Warp Speed but kept his shares. The records released by the House committee do not show how much the stake was worth.
“Documents recently obtained by the Select Subcommittee have heightened concerns that these advisors may have significant undisclosed financial conflicts of interest that, contrary to the administration’s public statements, have not been adequately addressed,” the committee’s chairman, Rep. James E. Clyburn, D‑S.C., said in a Sept. 21 letter to Advanced Decision Vectors LLC, a consulting firm that received the contract for the government’s work with Slaoui and other Operation Warp Speed advisers. Clyburn said the committee will subpoena the company if it doesn’t voluntarily provide more documents.
ADV’s CEO, David Harris, didn’t respond to messages seeking comment.
Congress should strengthen the federal ethics laws to root out this kind of corruption,” Sen. Elizabeth Warren, D‑Mass., said at a hearing on Wednesday. “And the first person to be fired should be Dr. Slaoui. The American people deserve to know that COVID-19 decisions are based on science and not on personal greed.”
Clyburn’s committee also released records that he said suggested conflicts of interest among three other Operation Warp Speed advisers: William Erhardt, Rachel Harriganand Carlo de Notaristefani. According to the documents, HHS certified that the companies in which the advisers have investments “are not involved in vaccines, therapeutics and diagnostic products developed to combat pandemic COVID-19.” However, several of the holdings that the advisers listed are in companies working on vaccines, treatments and tests for the coronavirus.
According to the records, Erhardt and Harrigan own shares of Pfizer, the current coronavirus vaccine front-runner with a $2 billion preorder from the government. Erhardt also listed holdings in Thermo Fisher Scientific, a diagnostics manufacturer that has received millions from the federal government for coronavirus testing materials; PhaseBio Pharmaceuticals, which has two clinical trials of drugs that could treat COVID-19; and Incyte Pharmaceuticals, which is also studying a possible treatment. The third adviser, de Notaristefani, reported a financial interest in Teva Pharmaceuticals, a manufacturer of the generic drug hydroxychloroquine touted by Trump as a coronavirus treatment despite lacking scientific support.
“HHS appears to be permitting these advisors to keep these holdings, along with any profits, by certifying that ‘the Government has determined’ the companies ‘are not involved in vaccines, therapeutics and diagnostic products developed to combat pandemic COVID-19,’” Clyburn wrote in his letter. “These certifications appear to be inaccurate.”
Baldassarre declined to comment on the certifications or answer other specific questions for this article.
ProPublica’s board chairman, Paul Sagan, is a member of Moderna’s board and a company stockholder.
https://www.propublica.org/article/trumps-vaccine-czar-refuses-to-give-up-stock-in-drug-company-involved-in-his-government-role
Here’s a story about the evolving SARS-CoV‑2 virus that underscores some of the core difficulties in addressing the coronaviru‑s pandemic with vaccines alone:
First, recall the troubling reports last month about a new variant of SARS-CoV‑2 that was discovered in the UK. The variant appeared to be more transmissible, although not necessarily more virulent, and had largely overtaken the new cases in the UK. This variant seemed to pop out of no where in terms of its mutational lineage, leading to speculation that it evolved in a single long-haul patient as the virus was battling the patient’s immune system. Adding to concerns was the news of another new variant in South Africa. This South African variant had a number of the same mutations found in the UK variant and was similarly proving to be more transmissible than the prevailing variants, resulting in this new variant causing almost all of the new cases in South Africa. Finally, it turns out the mutations identified as being functionally significant in the UK and South African variants were mutations on the spike protein component of the virus, which is ominous in terms of the ability of existing vaccines to tackle these new variants.
We now have a set of new updates on the South African variant. Largely troubling updates with potentially big implications for the existing vaccines. Three new studies on the variant were recently published, one out of the US and two out of South Africa.
The South African studies involve testing the responsiveness of antibodies taken from coronavirus patients last year in the presence of the South African variant. In one of the South African studies, they found that the new variant was either entirely or significantly resistant to the older antibodies.
The second South African study took the spike protein from the South African variant and placed in another virus (which kind of sounds like a ‘gain-of-function’ experiment). They found that the blood from 21 of 44 people who had previously had Covid-19 failed to neutralize this new hybrid virus. The only samples that were able to powerfully attack the virus were three samples from patients who previously suffered severe cases of COVID-19. So only 3 out of 44 people appear to have meaningful immunity against the spike protein of the new variant despite all 44 having had COVID-19 last year.
Finally, a study out the US took blood from people who received the Moderna or Pfizer vaccines and found that the three of the mutations in the South African variant on the spike protein disrupt the ability of those vaccine-induced antibodies to neutralize the virus. The US study didn’t find as dramatic a drop off in antibody efficacy as the two South African studies, but it was still a statistically significant drop. As the article notes, the lower drop off in antibody reactivity found in the US study compared to the South African studies may be due to the Moderna and Pfizer vaccines inducing a strong immune response than an actual case of COVID-19.
So we have three updates, all largely bad. There is one potential silver lining here: the mRNA-based vaccine platform should, in theory, allow for the development of new vaccines to address new variants much more quickly than previous vaccine development platforms. According to BioNTech’s CEO, Ugur Sahin, it would take around six weeks to design a new vaccine to address new variants if the current one ends up being ineffective. There would still be a hurdle, as Sahin points out, in the form of regulators that might still required months of safety trials, which is still far less than the years of safety trials used for previous vaccines. It points to a new era of vaccines: an era of the rapid development and deployment of vaccines with minimal safety trials, where the risks of the pandemic of deemed to be greater than the vaccine-related risks. And while that costs/benefit analysis might hold up under most circumstances, when you’re talking about something that’s going to be injected into the entire populace it only takes one ‘oops’ incident for a disaster.
It also points towards another grim possibility we could be looking at in the near future: the calls for repeated mass vaccinations of the entire populace. As frequently as new strains develop. It’s already very unclear if the US is going to be able to convince a large enough percentage of its population to take a coronavirus vaccine this year. What’s the public response going to be if mass inoculations are finally achieved and then we’re told everyone needs to go back for a second new vaccine months later?
More alarmingly, might we be looking at calls for multiple SARS-CoV‑2 vaccinations each year indefinitely? A real ‘New Normal’? It’s a possibility we can’t rule out. If that’s the case, we would just have to hope that SARS-CoV‑2 goes down the path of other coronaviruses and start off nasty but end up turning into a ubiquitous common cold virus.
Are we seeing the emergence of a quasi-permanent pandemic that starts off scary but eventually flares out? Or a real permanent pandemic and a permanent annual vaccine race? These are the kinds of questions raised by these new studies on the South African variants, and they all points towards the answer that this pandemic is far from over:
“If confirmed by additional research, the studies’ findings would suggest that winning the global fight against the coronavirus pandemic could require repeated inoculations and updates to existing vaccines, similar to what is done for flu shots every year.”
Winning the fight against the pandemic could require repeated inoculations and updates to existing vaccines, similar to what is done with the flu each year. It’s an interesting way to spin it since it’s not like humanity is really “winning” the fight against the flu. We’re just mitigating some of the damage. And it’s increasingly looking like that’s the likely end point for the coronavirus pandemic: a permanent virus that requires annual vaccinations. Like the flu, where last year’s flu antibodies may not be all that useful against this year’s variant. That’s the scenario the two studies out of South Africa strongly hinted at: COVID-infinity here we come:
And then there’s the US study that tested the efficacy of Moderna and Pfizer-generated antibodies against the South African variant. There was still a meaningful immune response, which is great news, but the variant did still seem to be more resistant to the those vaccine-induced antibodies. We don’t know if that’s due to the vaccine inducing a stronger immune response than an actual COVID-19 case. The study authors conclude that mRNA vaccines such as the Pfizer and Moderna shots “may need to be updated periodically to avoid potential loss of clinical efficacy,” which raises the question of how periodic would those updates have to be. Once every few years? Annually? Every few months? That remains to be seen, but keep in mind that it’s not just the vaccines that need to be updated. It’s everyone’s innoculation status that needs to be updated with the new vaccines too. Every vaccine update equates to a new struggle for mass inoculations:
Also keep in mind that the more frequently new updates are required, the less time there is to conduct safety trials on the updated vaccine. According to BioNTech’s CEO, it only takes them six weeks to develop a new vaccine in the face of a mutation. Are we going to be looking at a new regulatory regime for rapid vaccine roll outs with minimal safety testing?
Finally, a bit of possible good news: as researchers point out, while these studies may have troubling results in terms of antibodies, the studies didn’t ask the question of how T‑cells might respond to the evolving virus and it’s possible the T‑cells aren’t facing the same kind of challenges with the evolving virus that antibodies are demonstrably facing:
Will T‑cells save the day? Let’s hope so, but don’t count on it. It’s looking more and more like SARS-CoV‑2 is going to be a permanent part of our New Normal. Along with a perpetual SARS-CoV‑2 vaccine race and all of the social turmoil that comes with trying to convince people to take them.
So for all of the reports about the US’s troubled vaccine rollout and an apparent lack of any federal plans to coordinate the enormous undertaking, be assured officials will eventually get really good at rapid mass vaccination rollouts. They’re going to have a lot of practice.