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'The Never Again Plan': Moderna CEO Stéphane Bancel wants to stop the next Covid-19—before it happens

December 22, 2020

    Welcome to the "Lessons from the C-suite" series, featuring Advisory Board President Eric Larsen's conversations with the most influential leaders in health care.

    In this edition, Stéphane Bancel, CEO of Moderna, talks with Eric and OptumInsight CEO Robert Musslewhite about how his company designed a vaccine against the novel coronavirus—in just two days. They also dive into Moderna's collaboration with Operation Warp Speed, Bancel's "warrior personality," and his ambitious plan to develop vaccines against potentially deadly viruses before they strike humans.

    This interview took place on Friday, December 18, the same day FDA issued an emergency use authorization for Moderna's coronavirus vaccine.

    [Editor's note: The Daily Briefing is published by Advisory Board, a division of Optum.]

    Bancel
    Stéphane Bancel, CEO of Moderna

    Question: Stéphane, yesterday was a momentous day—for you personally, for Moderna, and for the country. And yet…I have to say you look remarkably relaxed.

    Stéphane Bancel: It's because I always live in the future, Eric. Last night, my team had a long meeting at 7:00 p.m.—not to celebrate, but to work over things. I'm always trying to get ahead of things.

    This is the first time we've lived through a pandemic, and we all know the consequences—from public health to mental health to economics. We're still in the middle of it, and it's going to be a very dark and hard winter. So we've got to keep working.

    Q: A dark and hard winter indeed, but now with a glimmer of hope. Let's start with yesterday's outstanding news: a 20-to-0 vote, with one abstention, in support of emergency authorization of your Covid-19 vaccine. I don't think it is an overstatement to call this an historic moment.

    Bancel: When I resigned from my last company, bioMérieux, to start on this journey at Moderna, I told my wife there was only a 5% chance it would work out.

    It just sounded scientifically nuts to say that you could make a pure, safe mRNA that you could inject into somebody to cause their bodies to make, on demand, whatever protein you wanted. But it was very clear that, if we could make drugs in this new modality, it would change medicine forever.

    That's because mRNA is essentially an "information molecule": It tells your body's cells what proteins to make. And once you have that capability, it's comparatively easy to change the message. You just change the zeros and ones—which is to say the four letters of life—but everything else is the same.

    The chemistry to make the mRNA is the same. The lipid, the piece of fat you put around it, is the same. The manufacturing process is the same. So you can design proteins to treat everything from cancer to rare genetic diseases.

    Q: Can you delineate how that's different from more conventional ways of making new drugs? How does it change the drug discovery/creation process?

    Bancel: One reason I was excited to work with mRNA was how it impacted the probability of success. My own experience in the pharmaceutical industry is that most drugs fail. And you know this well, Eric and Robert, you might work five to 10 years on something that just dies.

    That's not true in any other industry that I'm aware of. If Boeing runs into a problem designing a plane, it might take them five years longer than expected to finish, it might cost $2 billion more—but they're going to make the plane work, because it's just an engineering problem.

    But in pharma, most companies approach each drug as a brand-new scientific problem. If you're Pfizer, there is nothing you learn from Lipitor that you can apply to making Viagra.

    With mRNA, we can turn pharmaceutical problems into engineering problems. If you figure out how to make one vaccine this way, there is no reason why you shouldn't be able to make thousands and thousands, just by changing the message on the mRNA.

    And so it was very clear that, if we could find a way to make this safe, the probability of those drugs going from an idea in somebody's brain to working in a human was going to be staggeringly different.

    How Moderna designed a Covid-19 vaccine—in just two days

    Q: It's a remarkable human achievement to move from the genetic mapping of a novel pathogen to an approved vaccine in a mere nine months. One looks for analogies, and President Kennedy's 1961 "We choose to go to the moon" speech comes to mind. Fun fact—that declaration dates to May 25, 1961, while on another date 12 days earlier—May 13, 1961, a little-noticed article appeared in Nature magazine announcing the discovery of the mRNA technology. Very cool.

    Bancel: Wow, that is very cool Eric. I didn't realize that connection.

    Q:  So while mRNA has been around for a generation, your harnessing of the molecule for this use was, by any scientific yardstick, unprecedentedly swift. How did this come about so quickly?

    Bancel: One notion we have at Moderna is that, once we figure out how to make mRNA work in human cells, we can draw on academic and industry research to learn what various proteins do, and then we can turn those proteins into drugs very quickly.

    With COVID, our team actually designed the vaccine in two days in silico. We never touched the physical virus; we never had a sample of the virus. And we did it in two days.

    And the thing I'm most proud of today, the molecule that I hope today is going to be authorized by the FDA is 100%, atom-by-atom the molecule my guys designed on January 13 on a computer in two days.

    Q: That's extraordinary. No modifications?

    Bancel: Not one atom difference in that gigantic molecule. It's exactly the same.

    If we look back 20 years from now, I think we'll see this as a pivotal moment when we began to be able to make proteins to go cure humans. Basically what Covid-19 has done is accelerated medicine by four years.

    And I not only think this technology is going to be able, between the Pfizer vaccine and our vaccine, to impact millions of lives just in this country—but the impact of this new modality of medicine in the next 10, 20, 40 years is going to be mind-blowing.

    The inside view of 'Operation Warp Speed'

    Q: So in just two days, you designed the molecule you'd use in your vaccine. But that's still a long way from graduating to a tested and authorized drug. So I'd like to ask you about Operation Warp Speed and how you synchronized your efforts with the U.S. government, especially with the Biomedical Advanced Research and Development Authority (BARDA).

    Bancel: The partnership we've had with the U.S. government has been important. Moderna isn't like a lot of pharma companies that have a strong balance sheet and cash flow coming from their drugs. We've never had a dollar of sales. And one of the reasons we've been able to grow so fast is that, due to government support, we've been able to take a lot of business risk so that we did not have to take any safety risk.

    As a very simple example, usually a pharmaceutical company will wait for results and an FDA opinion on a Phase 1 trial before starting to make a Phase 2 drug. Because if your drug doesn't work or the FDA says "no," any money spent on Phase 2 will be wasted, right?

    Well, we started making the Phase 2 product even as we started dosing Phase 1 people. We were only able to do that because BARDA was paying for it. It allowed us to take a business risk that we, as a small company, could not have taken alone.

    Q: Beyond financing, how has the partnership with the White House impacted manufacturing and distribution hurdles?

    Bancel: In my opinion, one of the administration's best decisions in fighting this virus was to put in Dr. Slaoui and Gen. Perna as a leadership team for Operation Warp Speed. That brought together somebody from the industry and somebody with government supply chain expertise.

    And why is that important? Aligning the FDA and the NIH and BARDA and CDC is really hard to do. I can't do it as an outsider; I don't have any authority to do that.

    But Dr. Slaoui had that authority. He's talking to the industry, and he speaks our jargon. And he's able to hear from us what we need, then turn around to align all the government agencies.

    In normal times, it might have taken months to get them all into alignment, but we needed them to get aligned in hours or a day or two, because they were the critical obstacle delaying the work.

    A deeper dive into the vaccine's efficacy & durability—plus the open questions around transmissibility

    Q: Now that your vaccine has been granted emergency authorization, the headline figure is its 94% effectiveness in preventing Covid-19. But what do we know at this point about the durability of the immunity that's conferred? Or about the transmissibility of the virus from those who get vaccinated?

    Bancel: On transmission, we have preliminary data that was released publicly on Tuesday morning. We'll know more in the new year, but after one dose of the vaccine, we saw a reduction of around 60% in asymptomatic infections—which are a proxy for transmissibility of the virus. That's in addition to the 94% reduction in diagnosed cases of Covid-19.

    We don't yet have the data after two doses, but we believe scientifically it should be higher, because patients will have more antibodies and more memory and so on. But we need to, of course, wait for the data to know.

    So we're cautiously optimistic that our vaccine should be able not only to protect people who receive it from disease, but also protect the community by reducing spreading.

    Your question around duration, Eric—we just don't know yet. But we recently published evidence in the New England Journal of Medicine from our Phase 1 patients, based on three months of neutralizing-antibody data. And we saw that antibody levels are going down very slowly in all age groups, even in the elderly.

    What I can't tell you today is, how often will people need a booster shot to prevent infection? Is it going to be every two years for an 80-year-old person with diabetes, but every five years for a 25-year-old in good health? This we don't know yet. We just have to be patient.

    How Moderna went from long-shot to 'overnight success'

    Q: We've been talking principally about the last nine months, understandably, but I'd like to rewind to 2011 – when you took the CEO job at Moderna – for a second. You told your wife, "I give this a 5% chance. It's either going to fail or it's going to change medicine forever." At what point in the last decade, Stéphane, did you realize that this technology was going to be proven and corroborated as a new successful vector?

    Bancel: I think there were a few points in our history where it just hit me.

    One was when we made our first antibody. When we first decided to focus on antibodies, the team asked me, "Which antibody do you want us to make?" That's the good thing about mRNA: We can choose which protein we want to build.

    And I said, "Do Herceptin," the breast cancer drug. Not because we would ever make it commercially—there's already a great Herceptin product on the market—but because there's so much literature on the drug. If you put it on HER2-positive cancer cell in a petri dish, if you kill the cancer cell, you know the antibody is working.

    The team came back and showed me data from subcutaneous, intramuscular, and IV administration in monkeys. And in all three cases, they could take the blood of monkeys, put it on HER2-positive cancer cells in a petri dish, and kill them. The drug was working.

    Q: Why was that such a profound moment for you?

    Bancel: Two reasons. First, Herceptin does not exist in nature. It's a human-invented antibody created by Genentech scientists. So basically we were giving the instruction to monkeys to make an antibody that monkeys had never made before. And the first time we did it, all the monkeys made correct Herceptin.

    The second crazy thing scientifically is that we made that antibody in their liver—because that's where the technology was taking the mRNA. Your liver has never made antibodies; my liver has never made antibodies. It was not even known to science that you could make antibodies out of liver cells.

    And when I walked home that night, my head was spinning, and I felt like, "This is crazy. This technology has basically no limits."

    Q: Part of Moderna's success surely has to do with you and the culture you've built. Some of your colleagues have characterized you, very respectfully, as having sort of a ‘warrior personality'. Your personality seems to mirror the agility, the speed, even the iconoclasm of Moderna. Is that a fair characterization of you and of the company's culture?

    Bancel: Yes, I think so. It goes back to a very important piece, which is that we are very mission-driven. When I leave my house in the morning and I walk to Moderna, the only thing I think about is, "OK, how are we going to be the best version of Moderna to help as many people as we can?"

    But we've always understood we were a risky venture. Most startups fail, and in biotech, the failure rate is even higher. Noubar Afeyan, our chairman, who is a scientist and one of the co-founders of the company, has said since day one, "This will be either a zero-drug company, or we will make dozens and dozens and dozens of drugs."

    And so, I've always had this chip on my shoulder—not for me, but for this company, which was to say, "I cannot be the guy who failed this thing."

    Q: How do you think your leadership style has contributed to the company's success? I've heard you be self-deprecating and underscore that it's a team effort, and I absolutely get that. But what did you bring to this challenge that was key to where you've ended up today?

    Bancel: I figure a few things. I think I'm pretty relentless, OK? I'm not the type of guy who quits easily. I'm super-demanding, so if I think there is a better way to do it, I'll challenge you, I'll expect you to be bold and take a calculated risk.

    I'll also expect you to be extremely collaborative, because it's very clear to me that it takes a village to make a medicine. It takes a whole army of people with very different and very complementary skills, and sometimes it's hard for them to work together. But toxicologists and engineers from the process development group have to work together to figure out how to optimize the systems.

    Those are the expectations I brought to the table because of who I am, because of my personality, because of my own business experience. And I think I also brought the ability to explain to investors what Moderna could be.

    As I like to tell people, Moderna is an overnight success—10 years and $5 billion in the making.

    What's next: The 'Never Again Plan'

    Q: We've talked about the huge ramifications of this vaccine for this pandemic. But if we've learned anything, it's our hypervulnerability to future mutations of this pathogen (such as we're witnessing in the U.K. right now) or the emergence of other new-to-the-world zoonotic pathogens like Covid-19. What have you learned, Stéphane, that prepares us to respond more adroitly to the next crisis?

    Bancel: You're exactly right, Eric. And my next big mountain is pandemic readiness and outbreak readiness.

    Imagine a universe where we could have started Phase 3 trials of our vaccine in March, instead of Phase 1 trials. We could have had an emergency use authorization by July, and if we'd had a factory cranking 50 million doses a month that whole time—which is not a crazy-sized factory— we could have had 300 million doses available in the fall.

    For that universe to happen, you need two things. First, you need to do a lot of pre-clinical work on the top 20 pathogens that present the greatest risk of a human pandemic. You need to learn exactly the biology a vaccine needs to target, and you need to run your best vaccine candidates through Phase 1 and Phase 2 trials to get enough data on dosage and safety.

    In the case of the new coronavirus, we could have done this work based on MERS—you know, Middle East Respiratory Syndrome, which is another coronavirus. We could have identified vaccine candidates that targeted elements shared by both viruses, and we could have started directly on Phase 3 on March 16.

    Q: So that's the first piece of the puzzle. What's the second?

    Bancel: You need a big factory with raw materials in the basement, ready to go. Then in March we could have said, "OK, we're going to start making 50 million doses a month," and by July, we would have had 300 million doses. If the vaccine didn't pan out in Phase 3 trials, we would have wasted that money—but that's where a public-private partnership with BARDA can help mitigate business risk.

    Think about how different the fall would have been in that universe. And that's not science fiction. It's not even that expensive. It's like $20 to $30 million per virus, so even if you do 20 viruses, you're talking about half a billion dollars.

    Let's even imagine a billion dollars of investment. When you think about how much human suffering there has been in 2020, how much economic loss—it's so much larger. It's like one day of U.S. GDP that we need to invest to get ready for the next one.

    So that's my big next challenge. I've nicknamed the plan with my team: I've said, "This is the 'Never Again Plan.'"

    Gratitude

    Q: I want to ask a final question that we always ask when we're privileged to do these interviews. You've not only had a remarkable career, but you've had a remarkable nine months. As you reflect back on things, what are you most grateful for?

    Bancel: All the people that have helped me and helped us. So many people took a chance on us.

    There's Noubar, who took a chance on me and gave me the CEO job. The investors who, in the spring of 2012, gave us $25 million based on data in six monkeys. Pascal Soriot at AstraZeneca, who gave us a €250 million to get access to 40 drugs in March 2013.

    I can go on and on and on. I was at our factory in Norwood two weeks ago with a team, and it was 11:00 in the morning. I was talking to engineers about fixing a problem to scale up a process better, and their boss asked me at the end, "Hey, can you say they've done a nice job? Because they haven't gone to bed yet." They had worked all through the night before. And I didn't know it, because the guys were just full game-on.

    I have millions of stories like these of people doing the right thing for the mission of Moderna. This is, for me, an amazing story of human ingenuity and human collaboration.

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