Change Makers: Moderna's Stéphane Bancel on Passion, Advancing mRNA, Cancer, Rare Diseases, and COVID-19

John Whyte, MD, MPH; Stéphane Bancel


October 05, 2023

The CEO of Moderna speaks with WebMD CMO John Whyte, MD, MPH, about the potential of mRNA technology and much more.

This transcript has been edited for clarity.

John Whyte, MD, MPH: Welcome to Change Makers: The Future of Health. I'm Dr John Whyte, the chief medical officer of WebMD. Messenger RNA (mRNA) technology: Can it revolutionize medicine? My guest today is confident that it can. Stéphane Bancel is the CEO of Moderna. I had the opportunity to sit down with him at one of their state-of-the-art manufacturing facilities in Boston.

He explained why he firmly believes that mRNA science can create a new generation of transformative medicines, especially in critical areas such as cancer care and latent viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV). He also revealed why he chose to make rare disease a priority focus. Although we call these diseases rare, collectively they impact over 300 million people worldwide. Listening to him, I was struck by this fascinating perspective of drug development through the lens of someone trained as an engineer. If you're curious about the ever-evolving landscape of medicine and what the future holds for healthcare, this is an interview you need to watch.

Stéphane, thanks for joining me today.

Stéphane Bancel: Thank you so much for having me, John.

Whyte: I was fascinated by your website where it specifically says that mRNA could revolutionize — that's the word that you use —medicine. And it goes on to say it's all about the protein. Why "revolutionize"? Too strong a word or mot juste?

Bancel: I think it's the right word. Because if you think about it, since the first medicines were made available more than 100 years ago, what I describe as analogue medicine was the chemical structure of an aspirin or Prozac or Lipitor; are all very, very different. But what is really quite remarkable with mRNA is mRNA is an instruction; it's a piece of code. You're sending information to the cells, of course — natural information. That's how our body works to make proteins. And you instruct the cells to make the protein or proteins that you need. Even if a protein is very complex in structure, which could be a limitation in recombinant, because your body makes it, it knows how to do it. And so that's the piece that is really revolutionary: the ability to always use the same molecule, the same chemical structure, to send an instruction and then call your cells to do the rest.

Whyte: Well, let's take that to practice. And really, your pipeline focuses on that practice. Let's look at oncology. In oncology, everyone wants personalized medicine, precision medicine (less so for overall screening — that's a general population). But you really have made it an approach where you talk about this individualized cancer vaccine strategy. So, explain to our audience: What does that mean?

Bancel: Actually, we used to call it personalized cancer vaccine. But as we thought about it more, to me, a personalized medicine is a medicine that you adapt to my needs, to my mutation. But in that case, what we do is one step further; we design a medicine just for you. For example, if you were to have a lung cancer and if I were to have a lung cancer, there's a very high probability that the medicines we design for you and for me will be totally different. And the way we do it is to start with the genetic information of your cancer cell. So we read the entire DNA and we do the same thing with a healthy cell of your body. We look at the comparison of every base of the DNA, the free gigabytes of information, to figure out where you have mutation. And then we make a product just for you to educate your immune system, your T cells, to recognize the mutation of a cancer cell that they have missed so far, so that your immune system can go to work and get rid of your cancer.

Whyte: This is a new approach. This is something that has been in development for a while. As it iterates, how do you think vaccine strategy for cancer will look in 3 years, 5 years?

Bancel: I think we're at the beginning of a total paradigm shift in how we treat cancer and look at technology. I'm also fascinated because, as you know, I used to spend quite a number of hours in my career in diagnostics. I'm fascinated by liquid biopsy — the ability to find pieces of DNA of cancer cells in blood.

Whyte: And that's early on, as opposed to imaging, when we have to wait to 100,000 cells, 500,000 cells. This could be fragments early on.

Bancel: Exactly — very early on. As we all know, the key to cancer survival is getting it early. Think about pancreatic cancer, which most of the time is a death sentence. If we could find it really early on, at stage I or II, we could do something about it by designing a product just for that patient. That could drastically change cancer care. This is a few years away, between all products that now are in phase 3. It's possible that as the phase 2 data mature, because it's already very strong, that we could potentially go for accelerated approval. With the liquid biopsy progress and iteration of those technologies, I really think that in a 3- to 5-year timeframe, cancer care will look very different and will save a lot of lives.

Whyte: This is a way of thinking that other people have tried; why will you be successful?

Bancel: Because we have the right technology and we have the capital, but also the right partner, Merck, to do it. I don't have to explain to people the role that Merck has had in immuno-oncology. We have the right technology. As you know, John, cancer vaccines have been tried for decades. The success rate is 0%. They all have failed. And so when we saw the data that we showed late last year, and then more at the AACR meeting and more at ASCO again, it's working. There's no scientific doubt that this is working. We talk to the PIs and hear the stories of those patients who responded to the drug and the change in their life. This is not a fluke; this is not an accident. I think what's happening is that we have a technology that we can customize, because what the field has tried before was a shared antigen. But we know now that cancer cells have hundreds, sometimes thousands, of mutations.

Whyte: That's what makes it so hard to treat.

Bancel: Correct. But if you have to share an antigen like a chimeric antigen receptor (CAR) antigen or other antigens, that might not do the trick. We should never forget that the cancer has been growing in your body, and your immune system has not been able to take care of it. And so we really believe in this approach to the current technology. We stitched together 56 mutations of your cancer, but we know that we need only one that your T cell will recognize for the T cells to do their jobs.

Whyte: I want to turn to latent viruses, specifically EBV and CMV. I've been a physician for a long time; we've been talking about these viruses for quite some time. Why do you think we haven't made progress in effective diagnosis and treatment? And how are you changing that?

Bancel: That's a great question. I think the field of vaccine makers, as you know, have all tried to do a CMV vaccine, but they failed. And with EBV they failed. Going back to your word "revolutionize," the technology allows to follow natural biology. What do I mean by that? The CMV, EBV, and all related viruses are a very complex protein structure. One of the antigens that is important for CMV to get into human cells is the pentamer. As the name says, it's five proteins that have to come together in a special structure. People were not able to make that structure using recombinant. But if we can make the five mRNAs coding for each of the components of a pentamer and put it in the cell, then the five proteins will be made. We've shown and published that. What is beautiful about virology is that they will assemble to make the pentamer, like the virus does in your body when you get a natural infection. We have managed to make extremely complex protein or antigen to prepare your immune system to be ready for it in case you get a natural infection. And that's what I think is a big scientific breakthrough with mRNA in latent viruses, which is why CMV, which is now in phase 3, it's almost fully enrolled. The phase 1/phase 2 data are very impressive — both gB antigen and pentamer antigen. The same thing with EBV. I think we have a serious shot at bringing to patients prophylactic vaccine to prevent those infections. And it's not only the short-term consequences like birth defects with CMV and mono with EBV. What we're very excited about concerns long-term complications for human health, because those viruses, once in our body, are in our body forever.

Whyte: And that's the impact of treating these early on, hence why we're calling them latent. It's a terrific point. We did an impromptu tour a little earlier when I came in and had a quick discussion around rare diseases, and that's what I want to come back to. I was very excited to talk to you about it today. Just for reference for our viewers, there are 7000 rare diseases and 300 million people impacted worldwide. So we call it "rare," but it has a significant impact on people's lives, and only 5% of the 7000 have approved indications. Why did you decide to make this commitment to rare diseases? Is it because of the platform that you described early on?

Bancel: The commitment first is to the families and to the kids. I have kids, and it's a thing I've always discussed with my wife since thinking about joining Moderna, when it was just an idea and not much of a company. It was always clear that mRNA, if it worked safely in humans, could be a great technology for rare disease, because a lot of those rare diseases are coming from protein deficiencies; kids have the wrong instruction in their DNA from mom and dad, inside the cells. If you think about the recombinant technology and what happened with enzyme replacement therapy that has helped so many families, those are proteins that are secreted and are basically turning in your body, in our blood. But a lot of rare diseases are basically a genetic mutation of protein, intracellular — inside the cells.

Whyte: So you're changing the instruction rather than aiming for replacement.

Bancel: Correct. At this stage of technology, we're not aiming to do gene editing or change the DNA of a patient. If a kid has propionic acidemia, a protein deficiency inside his liver, we're trying to get him on an IV, for a technology of lipid that is different from the one used for the vaccines. It's to get the mRNA inside the hepatocytes earlier to express the protein that the kid cannot make. The animal models have been very, very exciting. And recently, in the spring of this year, we shared that as we were going up in dose — carefully, for the safety of those kids in the studies — that we were able to reduce by 75% already, including the low dose that most probably in the phase 1 and 2 was not efficacious, 75% reduction of medical decompensation events. Those kids are kept alive by the heroic work of our doctors and nurses that take care of them, as well as the parents. Every time they have a decompensation event, they might end up in the hospital, in the ICU, and some might end up dying. So it's very exciting that the technology enables us to basically give them the right protein, regardless of where it is in the body, regardless of how complex it is. If you think about the propionic acidemia, for scientist geeks like we are here at Moderna, this is a protein deficiency in the mitochondria of the hepatocytes. We have to get the mRNA specifically to the hepatocyte. Once you get into the hepatocyte, you make the protein, which is a very complex protein; it's actually two mRNAs. And then it has to be chaperoned inside the mitochondria of cells so it can have its clinical impact.

Whyte: But you've also focused on ultrarare diseases, which some estimate is literally one in a million, these "N of 1" trials. We talked about my own experience at FDA; how do you prove safety and efficacy when you literally have an N of 1?

Bancel: We think we're going to bring this platform technology, where we always use the same chemistry for all of those rare diseases in the liver. I'm told that there are around 1500 rare disease in the liver because the liver is such a big protein machinery for the human body. Every product we will make for the liver will have the same lipid to protect from blood degradation and to take the amount inside the hepatocyte. The only difference between drug 1 and drug 2 will be the order of instruction — the nucleotide on the mRNA; the chemical matter we give in your body will be the same. So from a safety standpoint, this is a huge de-risking vs the small-molecule world, where every chemical molecule is a chemical with a different structure. The other piece is what we're doing in cancer, which is why this technology is quite interesting in terms of how you can connect dots; it's all information based. As we discussed a minute ago, I said that if you have lung cancer and if I have lung cancer, we'll make a different molecule for you and I. So there's already a path with the agency that has been tried in cancer, to have the approval not of a drug but of a process. We think we can prove to FDA that every time we make a product for genetic information, we have the same outcome in the end, and so we would for cancer. I think this technology down the road is usable in the same way for ultrarare diseases.

Whyte: Just by the way that you're explaining all of this, I have to ask: Have you trained as an engineer?

Bancel: Yes.

Whyte: When I've talked to other people interested in drug development, a lot of them are physicians, and it just seems like a different mindset. Do you feel that you have a different mindset with your engineer training, that that's how you're approaching these problems and treatments and diagnostics?

Bancel: As engineers, we're trying to find solutions to problems, and so we always try to design the drug backwards, starting with What's the biology?

Whyte: Reverse engineering?

Bancel: Exactly. We should look at what's happening for diseases like cancer, the mutation of DNA and the role of the T cells. How can we use these very malleable, flexible technologies to do what is required for having the right biological impact? I think the engineering mindset has helped us figure out how to really customize and reuse bricks of technology — a little bit like a Lego. The piece I've always loved about it is that we make natural protein. We talked about aspirin and Prozac and Lipitor earlier; those molecules that have been had by millions of people do not exist in nature. So when you go after discovering medicine in the traditional pharmaceutical world, you try really hard to make a molecule that doesn't exist in nature, working in a human body while being safe.

Whyte: We're in a big building here — lots of buildings; I joked about finding the right entrance. But when you came here in 2011, it wasn't a very large company. You were running a French diagnostic company as the CEO. Why did you choose to come here? I've heard from various people that you were employee number two. How many employees are there now?

Bancel: We're getting close to 6000. The reason for joining is quite simple. When I first heard about this idea of using mRNA as a drug, I said to the founding team, which was a group of academics from Harvard and MIT, "You're crazy, right? This thing is never going to work safely in humans." The more I thought about it over the coming days and weeks, the more it became clear to me that if we could find a way to make this work safely in humans, it will fundamentally change — it will revolutionize, to go back to your word —medicine. I use the recombinant industry as a mental model. If you think about what recombinant was in the 1970s, with tiny Genentech, tiny Amgen starting, going after this new technology that pharma had no idea how to use… And now think about what it has done for patients in the past 50 years. You can start with growth hormone and insulin, and then the PD-1s and so many other drugs in between; it has really changed hundreds of millions of lives. And so there was a thinking in 2011 that there will be this new technology that potentially could be more profound because it's an information molecule.

Whyte: You were CEO in one country and had to bring your family to another country so you could work for a very small company as employee number two.

Bancel: It was just this idea of You will change medicine forever. I told my wife that I would rather take a 5% chance to build a company that will change medicine forever, in a very profound platform like this, than take a 90% chance to be the average biotech company that maybe might get one drug to market in the next 20 years. That was the bet. All my friends said, "Don't do it." And I still did it. I'm very thankful because the last 12 years has been an incredible journey. Of course, there's COVID, something that none of us could ever have planned — a pandemic. It has been remarkable to see the commitment of a team and the teamwork with our partners.

Whyte: Let's talk about COVID. Behind us here, we have all these vials that represent the map. Has COVID vaccination changed how we think about drug development?

Bancel: I think it has in at least one obvious way, which is that when there is a big medical need, if we all come together — the different players in the industry (because we could not have done it alone), regulators, and government officials (because the NIH had a big role, as you well know, as well as the CDC) — we can do extraordinary things. I think if you had talked to any leaders in any of those facets of healthcare in December 2019, and you told them that collectively we can get several high-efficacy vaccines in less than 12 months to the finish line by still doing phase 1, phase 2, phase 3, nobody would have believed it because it was such a huge challenge. Back then, when we started running after the virus, we were at war with this virus. It was literally killing thousands of people every day. Every day mattered, every hour mattered, and the energy, the commitment — it was personal for everybody. I used to come here to Norwood [Massachusetts; location of a Moderna manufacturing site] regularly. Sometimes I would visit in the morning, and I would see engineers who had been there all day the day before and worked through the night. They'd go to locker room, take a shower, and then would get back to work again. It was personal for everybody because there were kids locked at home. A lot of the time, the spouse was not working, we were worried about parents, uncles, and aunts — some got hospitalized and some died. So it's very personal. And the collaboration was amazing. Sometimes we'd have two or three meetings with FDA in the same day, which would never happen in normal times. Sometimes it would even be on a Saturday night. The energy and the commitment of so many people are what made it possible.

Whyte: Did it revolutionize medicine?

Bancel: I think it was the first step in in revolutionizing medicine in terms of 1 year to launch. The fastest vaccine before was 4 years to launch. We think about what the world would have looked like for over 3 years with a pandemic. Of course, it would have slowed down, as we saw in 1918, with more and more people infected and natural immunity — and, unfortunately, a lot of people dying. But it's the beginning of a revolution. I think it has shown people that this technology can change everything. And it's what we do believe at Moderna. It will change everything.

Whyte: We're starting to see cases increase. Right now, there's talk about whether people need boosters in the fall. What are your thoughts on what people need to know today?

Bancel: COVID is here to stay with us, we believe, forever, like flu; we don't believe that this virus is going to disappear in a year or 6 months or a few years. It keeps on evolving, like flu. I think flu is a very good mental model for people to have who don't necessarily understand the science like you do. We need to adapt the vaccines to where the virus is and is evolving. That's what we have done. FDA has been very clear — in the spring with a new strain of COVID, the XBB — that they wanted [an updated COVID vaccine]. We worked on it all summer. We have tens of millions of doses in a warehouse ready to go. We're waiting for the green light to be able to ship them to pharmacies, and for CDC's recommendation of who should get them. But I think the mental model that doctors, healthcare professionals, and consumers should have is: You need to protect yourself. And I think we all have a civic responsibility to protect each other.

Whyte: But how do we battle this COVID fatigue that we hear from people, as well as the misinformation? What's your counsel there?

Bancel: There are data from clinical study that it's safe to get the flu shot and the COVID shot. One of my personal recommendations is that if you get a flu shot, get the COVID shot in the other arm on the same day. It's safe, it has been shown, and as CDC recommended. One of the cool technologies that we are working on is to combine COVID and flu into a single shot. We're also working on a respiratory syncytial virus (RSV) vaccine, as you know; we filed to the FDA an RSV vaccine that I hope will be approved soon. The data are very, very strong. And we also want to combine this into a single dose. So, ideally, in a couple of years, you will be able to go to your local pharmacy and get your COVID, flu, and RSV vaccinations in one shot, and then spend a nice winter where you don't worry for your health or about other people. That's what we want Moderna to do with this technology — make your life easier and protect you.

Whyte: If I went around and asked the other executives, "What's Stéphane's leadership style?", what would they tell me?

Bancel: I think they would tell you, "He is very mission driven." There is not a meeting, I think, where I don't point to the wall. In conference rooms, we have the company's mission statement painted on the walls, to remind people that we are here to maximize the impact of this technology and the science to help as many lives as we can. I think they'll tell you, "He is really impatient." Because for me, every day that we waste, where we don't do our best work, in 2 months or 6 months or 5 years, somebody will get hurt because we didn't do our best work, and it's on us.

Whyte: You took a chance in 2011. It was a 5% chance, but you wanted to make an impact and revolutionize medicine, as we've discussed. And in 2022, you were given a Chevalier (Knight) of the Legion of Honor, which is France's highest distinction of military and civic accomplishment. How did that make you feel?

Bancel: Very humbled. Every time I got recognized in the past year or two post-COVID, I've always told whichever organization was giving me a prize that it had to be for the team because I didn't make the COVID-19 vaccine by myself. We are literally hundreds of people, into the thousands, each playing a very important role because, as you know, making medicine is a team sport. The piece that is humbling is, in a country where we would like to see more entrepreneurs in France, I think having an entrepreneur recognized for contribution to society is a good example, I hope, to give to the next generation — of leaders, engineers, doctors, scientists — the courage and some time to take a big leap of faith, which I did. It was a crazy idea, using mRNA to inject in people. There's a lot of amazing science happening every day around the world. I really hope that we have more entrepreneurs turning those into products so that we can help a lot of people.

Whyte: Should I have been calling you "Sir"?

Bancel: No, I love this about the US — the informality. "Stéphane" is perfect.

Whyte: Well, Stéphane, thank you very much for taking the time today.

Bancel: Thank you so much.

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