One after a vaccine developer at a round table at the White House, which was convened by President Donald Trump in early March, lined up the product as a viable solution to the global-spreading coronavirus, killing Americans.
John Shiver, head of R&D for vaccines against Sanofi Pasteur, said he could have a product ready for the clinic in a year – perhaps a vaccine for the public in as few as several years.
Trump seemed disinterested.
Next was Lenny Schleifer, founder and CEO of Regeneron – which aims to conduct clinical trials this summer – who talked about pumping 200,000 doses per month of its therapeutic vaccine from its factory, which started in August, "if anything goes Good."
This got Trump's attention. He leaned over the table and interrupted Schleifer in the middle of the field.
"So that process would be faster than John's?" he said, pointing to Shiver.
"That would be it," Schleifer said, adding that the process could take "weeks to months."
The only way to top it off was to start talking about days, and that's exactly what the next CEO did.
Moderna Inc.'s Stéphane Bancel looked over the table at the country's top infection control expert, Dr. Anthony Fauci, saying he is "very proud to work with the US government and to have already sent, in just 42 days from the sequence of the virus, the vaccine ours to Dr. Faucy's team at NIH. "
The French-born Bancel further said that he only needed "a few months" to start phase two in a three-part clinical trial of the type that characterizes vaccine development. (The whole process often takes more than a decade.)
Trump seemed to set everything else apart from the conversation of the time.
"So you're talking over the next few months, do you think you can get a vaccine?" he asked.
"Correct. Right," Bancel said, raising a hand to acknowledge that Fauci was changing his chair across the table. "With phase two," Bancel clarified, just before Fauci interrupted, in favor of Trump: "You don't want a vaccine. You want a vaccine to be tested."
For some observers, it was a classic Bancel performance – a rare audience that glimpses his uncanny ability to say the right thing to the right people at the right moment.
However, his followers say he did what he always did: to let the achievements of the Mother speak for itself.
Regardless, it turns out that Moderna had an edge. The researchers had already collaborated with researchers from the National Institutes of Health on a vaccine for another coronavirus, Middle Eastern Respiratory Syndrome (MERS). So when Chinese scientists released the genomic sequence for the new coronavirus – SARS-CoV-2, which causes the deadly disease known as Covid-19 – in mid-January, they had a jump start.
Moderna was created in 2010 and has never brought a product to market, or received any of its nine or so vaccine candidates approved for FDA use. Nor has it ever brought a product to the third and final phase of a clinical trial.
And yet for the moment, it represents one of the country's – and possibly the world's – best hopes for a return to normality that slipped away when the microscopic enemy put civilization to silence.
Large funding injected into the vaccine course
The effort received another boost April 16, when the federal Biomedical Advanced Research and Development Authority (BARDA) awarded Moderna up to $ 483 million to accelerate the development and production of the vaccine. That makes up about half of the federal agency's budget, with Janssen Research & Development – part of Johnson & Johnson – receiving $ 456 million, and a third company, Sanofi, receiving up to $ 30 million.
As it happens, although Moderna is not a household name, it is a company with a storied history.
CNN Investigates interviewed more than 20 experts and former employees for this story and found that although some researchers expressed optimism that Moderna might pull it off, others voiced criticism about the hype the company has generated over the years, as well as what has been described as a caustic work culture.
Others raised concerns about science, or challenged the wisdom of the federal government-sanctioned shortcuts in the ongoing clinical trial, particularly the FDA's approval to shine on animal studies that normally precede injecting an unproven vaccine to healthy people.
Dr. Joseph Bolen, who served as Moderna's head of science and president of research and development from 2013 to 2015, believes it was reasonable to give Moderna a shot, but was amazed by BARDA's huge grant – up to $ 483 million – and called it a " great effort."
"I don't know what your thoughts were," he said. "Why so much? … I just don't know. When I read it, I was quite surprised."
Dr. Tal Zaks, Senior Consultant of the Mother, acknowledged that the company does not have a product on the market, but said the government's decision was wise.
"We are a young company with a new technology, and so far we have not brought anything to full license," he told CNN. "But if you look at the building blocks of what we have been able to demonstrate over time – from preclinical through our early clinical data – this is a very promising technology."
Moderna is in front of the herd
Moderna, Inc. – originally called Moderna Therapeutics – was founded on a big idea that would disrupt the pharmaceutical industry.
The vision is to utilize a new technology that synthesizes messenger RNA, or mRNA – basically a manual in every living cell to make protein – to ask the human body to make its own medicine. The hope has been to find "transformative" treatments for heart disease, metabolic and genetic diseases, kidney failure, and even cancer.
BARDA said it plans to fund a number of approaches.
"More than one vaccine is likely to be the solution," a spokesman for BARDA said in an email. "Strangely enough, Moderna was the first to enter the clinic with a vaccine."
Over the years, Moderna has sold investors on the revolutionary potential of medicine. Bancel has been the main narrator for the company's intoxicating history.
Ambition, secrecy and money have earned Moderna critics
But the Mother's unbridled ambition, reputation for secrecy and commitment to venture capital have hurt them.
"Offers don't validate science," the op-ed said. "Biotech is strewn with examples of large money purchases or licenses that have been written off or abandoned later."
"They have been a bit dense with their data," says a former BARDA official who now works as a biotechnology expert at Biologics Consulting and has worked with Moderna. "And I interpret it because the results so far have been disappointing."
In a rare interview, Noubar Afeyan, one of Modern's four co-founders and current chairman, told CNN that the company's reputation for secrecy is misunderstood.
"They are mistaken for the duty of confidentiality for ambiguity," he said of critics, noting that the company did not publish in the first few days because it had nothing to publish – it was in the experimental phase.
But Matthias John, a molecular biologist who was a group leader and senior scientist at Moderna for nearly four years ended in 2016, remembers that he was asked not to publish even when he had good data.
"They really had this fear of revealing results," he said, adding that the company was concerned that it would allow competitors to capture their innovations. "It was just a shame. … We had amazing data back then."
Critics call for more skepticism
A former employee, who worked for the company for three years, ending in 2019 – most recently as director – called the comparison "absurd."
"I think Moderna has a strong compliance culture," said the former director, who spoke on condition of anonymity, saying that the biotechnology industry is a small world and that he did not feel comfortable speaking. "They are very driven. They have a strong vision, they work very hard."
But a former company manager had a more mixed question on the issue. On the one hand, he said, science is on a "good basis."
"They really push the boundaries to understand RNA," said the former leader, who requested anonymity because he is still working in the field.
In his view, however, Moderna is a company that "believes in its own history, spins its own history and has managed to convince many investors – in-biotech investors and other non-biotech investors – that it is true," he said. . "I think (people) should approach it with a little more skepticism."
Mother's turbulent start
In its early years Moderna was a chaotic place. Over a decade, the work size has expanded from four employees to more than 700.
But there were adult pains, some of which centered on Bancel, the only managing director the company has ever had.
Afeyan, a venture capitalist with a doctorate in biochemical engineering from MIT, had tried to recruit Bancel to lead other projects, but Bancel – former CEO of a French diagnostic company – had rejected him.
When Afeyan asked him to join Moderna, the idea was too big for Bancel to resist. The holder of a Master of Science in Chemical Engineering from the University of Minnesota and an MBA from Harvard Business School began in 2011.
The former manager, who stepped down in 2016, remembered that Bancel seemed to have two versions of himself: the quiet public persona who speaks and appears on TED Talks, and the private version in corporate meetings.
"What you hear at business meetings is stuff like this, 'What are you wearing? It's completely silly … You said only six to nine months; I need it in five. & # 39; "
Dr. Suhaib Siddiqi, a chemist who briefly served as Moderne's former head of chemistry in 2011, said Bancel was "unfriendly" and "arrogant" and punished technicians for failed experiments.
"Ninety percent of things in science fail – that's how inventions are made," Siddiqi said. "When it failed (at Moderna), he just shifted the blame to the technicians and fired them."
Bancel disputes the characterization.
"Science is complicated and many things fail," Bancel, who rejected CNN's interview, responded in a written statement. "I don't remember an employee being fired since we started the company because of the science failing. If that had been the case, most researchers would have left the company and the company couldn't have reached the point it is."
He added: "We are creating a new class of transformative mRNA drugs to improve patients' lives. When there is an opportunity to help patients, it is important with each day. So what we do is urgently because patients are waiting. We are privileged as part of a broad ecosystem of academia and industry researchers that extends the understanding of mRNA. "
Some former employees spoke in defense of Bancel.
"As a person I like him," said Matthias John, the molecular biologist who left in 2016. "He's a bit of a fanatic. But he's not, in my opinion, a cheater or a pretender. It's his personality – he's pushing hard and he expected everybody would push in the same way. "
The former director who retired in 2019 said Bancel has brought in a management team with experience in biopharmaceutical development that has "hardened its intensity."
Rossi said he struck his head with Bancel, and that the company and its investors had a way of honoring the ideas of the researchers, including his own – a claim that Modern's management denies.
But Rossi, who later went on to become associate professor at Harvard Medical School and is now the CEO of another biotech company called Convelo Therapeutics, said he believes in the technology. He continues to have a financial stake in the company.
"I'm very optimistic," he said. "It's still going on the exact concept it was founded on."
Rossi, who said he has heard that the culture at Moderna has become soft, added that at some level the chain's scenic nature made sense.
"I founded the company because I wanted to influence human health," he said. "The CEO's job is to make money for investors."
Afeyan, chairman of Moderna, defends Bancel fiercely. He told CNN that the characterizations of Bancel as a gifted fundraiser are misplaced and even "derogatory," and said it is a way for detractors to lubricate him with faint praise.
"He is a skilled team builder, he is a skilled product developer, he is a skilled strategist, he is an accomplished partner forger … he is all these things," said Afeyan. "To get fuel for all this, he must have come up with money, and we did it, in a way that is unique in the biotechnology industry. Also of tenfold. That's why he has detractors."
The great offerings that shaped Moderna
Afeyan said it's true that Alexion's experiments showed animal toxicity, but added that Moderna has since changed formulations and in human studies, "we haven't seen any of it."
Moderna gradually began to shift its focus to vaccines. Experts and former staff say that the progress of therapeutics was much slower and more difficult to arrive at where it could be used as promised in humans. Messenger RNA activates the body's instinct to get rid of the foreign invader, which works better for single-dose vaccines, but creates safety concerns for long-term use in chronic diseases.
Jeff Ellsworth, who served as Mother's former senior director of preclinical pharmacology and head of rare genetic diseases until he retired in 2013, remembers sitting around a white table in the office with two business executives and discussing the data used in animal studies for medicine intended to treat rare genetic diseases.
"We all looked at each other and said, 'Oh. We should probably be a vaccine company, "because these things stimulate antibody responses," he said.
Rossi said, "It's the perfect technology for the threat we're facing."
"Most of the biotechnology community didn't value vaccines," Ellsworth said. "It was very difficult to get those things forward. Because people said, '# Vaccines, no one's going to pay for it – it's not that dangerous.'
"In our lifetime?" Cramer asked.
"It's actually happening right now," Bancel replied. "We compare all DNA letters … about a cancer cell and a healthy cell, and deduce from what we need to do in our product, just for cancer."
"It's almost science fiction, what you have to do," replied Cramer. "I think it's incredible."
The mother's valuation ballooned to $ 7.5 billion – up from the already impressive $ 5 billion from a year and a half ago.
Then came the new coronavirus and Covid-19, which has killed nearly 63,000 Americans since February and 233,000 people worldwide.
For the world, it was a disaster. For Moderna, it arrived just in time.
As the economy was on the mind, shares in Moderna rose in February when news of the vaccine came. They shot up again – by more than 24 percent, to $ 26.49 – March 16, the day the clinical trial with the vaccine made headlines. The stock price continued to rise and rocket again April 17 – with news of the federal government's nearly half a billion dollar investment – to over $ 45. The valuation climbed to $ 10 billion.
The vaccine pipeline is a funnel: & # 39; Very few things survive & # 39;
Trying to bring a vaccine to the market is trying to beat the odds.
Dr. Myron Levine, professor and expert on infectious disease at the University of Maryland School of Medicine, warned that most vaccines fail.
"I've been in this business for a very long time – half a century," he said. "A vaccine cord is the shape of a funnel. Many things go on one end; very few things survive."
Still, Levine believes that Moderna can make a breakthrough.
"There is a really good chance that this will be the moment for the RNA vaccine – they have been improved and fine-tuned," he said. "I hope and pray that they work."
Moderna did not invent the mRNA approach, but is the company that has "cornered the market" on the idea, said the former leader who resigned in 2016.
"Henry Ford wasn't the first carmaker, but he managed to scale more efficiently," he said.
The science of messenger RNA is complex, but the potential benefits of frequently identified bottom lines are easy to understand: security and speed.
Conventional vaccines involve injecting a small portion of a weakened or dead virus into the body to stimulate an immune response in the cells.
Coronavirus spike-protein lookalike would then be produced by the body's own cells. If all goes well, the body then counteracts the "intruder" – the synthetic antigen created by a person's own cell – with antibodies.
The technology "teaches the human body to recognize the virus by teaching the body to make extracts of the virus on its own," says Zaks, Modern Medical Director.
On January 11, Chinese scientists released the genetic sequence of SARS-CoV-2, a string of 30,000 characters with the letters a, u, g and c.
Mainly due to the ongoing collaboration between Moderna and NIH, the process of designing mRNA for delivery became lightning fast. In fact, it only took 42 days, as Bancel told Trump.
Officials at the National Institutes of Health are bullish.
"Much of our work we have done in the past has largely driven us into what we call a quick response," said Dr. Kizzmekia Corbett, a leading coronavirus research scientist at the National Institutes of Health, in a recent interview with CNN's Anderson Cooper and Dr. Sanjay Gupta. "The really interesting part about this is that we have a collaboration with Moderna," she added.
A spokesman from the National Institute for Allergy and Infectious Diseases – a branch of the NIH – said that Mother's Vaccine Platform is well suited to respond to new outbreaks such as new coronavirus.
It "can be produced faster than with many other vaccine platforms," says Judith Lavelle. "As the genetic information on a given growing virus becomes available, researchers can quickly select a sequence to express an immunogen in the existing mRNA platform."
Science has its skeptics
But some experts are skeptical of science.
First, in the rush to get started, the FDA released Mother's RNA vaccine – called mRNA-1273 – essentially shining on animal testing that usually precedes clinical studies in humans. Given the nature of this emergency, they happen in parallel.
Siddiqi said this is cause for alarm.
"I wouldn't mind [vaccine] to be injected into my body, "he said." I would like to ask: Where is the toxicity data from the laboratory? "
Professor Nikolai Petrovsky at Flinders University in Australia, who works with Oracle to use computer models and AI technology to develop a Covid-19 vaccine, is concerned about the mRNA tests, and insists the US government has taken an unprovoked vaccine and "said (it) straight into people."
"It's a double game," he said. "An untested platform for a new disease without animal testing."
But while these experts thought dosing humans before animal experiments could be questionable in practice, Zaks of Moderna said it would be "unethical to wait," given the urgent pace of the pandemic.
The FDA said in a statement to CNN that it "could not comment on specific unapproved products." However, it said that when assessing the need for a vaccine study, the agency considers the relevant data. "If the FDA's evaluation of this data supports the initiation of human studies of a candidate coronavirus vaccine without first completing further toxicology studies, the FDA would consider allowing such human studies to continue."
Petrovsky also noted that while NIH and Moderna were working on a MERS vaccine, they had not collaborated on a SARS (Severe Acute Respiratory Syndrome) vaccine. MERS is "quite a different virus than SARS and Covid-19," he said. "MERS bonds are different receptors, different disease patterns. … I would be much more comfortable with SARS data."
Petrovsky said that although RNA vaccines are very fast to make, there is evidence that they will work poorly.
"I det siste har vi sett at de har dårlig immunogenisitet, noe som betyr at de ikke stimulerer immunforsvaret særlig godt," sa han.
Saaks: "Vi har demonstrert verktøyet til å generere riktig type immunrespons gang på gang i flere fase en-studier."
Utfordringen med et farlig fenomen
Et hyppig hinder for vaksineutviklere er et fenomen kjent som sykdomsforbedring, der vaksinen faktisk fremmer infeksjonen og gjør sykdommen verre.
"Det verste mulige du gjør er å vaksinere noen for å forhindre infeksjon og faktisk gjøre dem verre," sa Fauci på en briefing i Det hvite hus i forrige måned.
Dette fenomenet understreker viktigheten av dyreforsøk, sier eksperter.
Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, worked on development of a vaccine for SARS. Some of the animals he vaccinated wound up sicker than the ones he didn't vaccinate, once they were exposed to the virus.
"If there is immune enhancement in laboratory animals vaccinated with the Moderna vaccine, that's a showstopper," he told the news organization.
A Moderna spokesperson said the company has not seen signs of enhanced disease in animal trials with the MERS vaccine that it was developing with NIH.
"Enhanced disease is a clinical finding that is very rarely seen," she said in an email.
Potential setbacks fall into two broad categories: the vaccine isn't strong enough to produce an immune response or the vaccine causes safety issues.
Anderson added that there is a "theoretical possibility" that the vaccine could trigger an "enhanced immune response" that actually worsens the illness.
Adjuvants stimulate the body's immune system to react to the vaccine antigen — the molecules that trigger an immune response in the body. In other words, they boost the body's immune response.
"Typically, what you see in any vaccine if they use adjuvants, they clearly identify that and say this is the purpose of using in the vaccine formulation as an adjuvant," said Schrum, who is no longer with the company. "In that one [Moderna], I just don't see that."
Moderna confirmed that it is not using an adjuvant.
"We have not used adjuvants in our vaccine clinical trials," the spokesperson wrote in an email, adding that the trials have shown that Moderna's vaccines induce an immune response similar to that seen with natural infection.
The former BARDA official told CNN that Moderna generates a lot of "hype" for an organization that has never entered the third and final phase of a clinical trial for a drug or vaccine.
"I don't think it's misplaced to — I want to say question — but have some healthy skepticism about the current efficacy of their technology," the expert said.
Ian Haydon of Seattle is one of the trial participants who volunteered to take a shot in the arm in April. He said that so far — after a couple of weeks — aside from a sore arm for a day or two after the injection, he has experienced no symptoms.
"I'm eating normally, I'm sleeping normally, I feel fine," said Haydon, a 29-year-old science writer and a biotech consultant.
Far from assuming he's immune, Haydon said he's being more careful than ever.
"Now that I am a subject of study, now would kind of be the worst time for me to get sick with the coronavirus," he said. "I'm keeping locked up at my house, only going out to get groceries, hand-washing, wearing a mask, just like everybody should be."
Petrovsky said the United States is unique in how it has poured so much money into "one experimental technology."
"The danger here is … if the US just backs one or two horses and they fall to the back of the pack, we're not going to have an effective vaccine in the US anytime soon."
But Zaks says Moderna has delivered on its promises to US officials about its coronavirus vaccine, saying, "When our CEO said that we would get this fast into the clinic, we did."
That, he said, combined with the company's potential, is why "the US government stepped in and picked our platform as one of the major investments that Tony Fauci and the team are making in. And I think if you stay in tuned, you should expect to see us be able to deliver on that."
CNN's Scott Bronstein and Drew Griffin contributed to this report.