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Stephane Bancel, Moderna | mRNA Therapeutics, Boston Biotech Mafia, AI Biotech | E35

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Philip Hemme
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We’re with Stephane Bancel, CEO of the US mRNA giant Moderna. The company’s 15-year trajectory has taken it from the startup seed stage to a commercial heavyweight with three mRNA-based products in the market 🧬

We go in-depth into Stephane’s leadership style and background before delving into Moderna’s research and the evolution of the mRNA space.

⭐️ ABOUT THE SPEAKER

Stéphane Bancel joined mRNA therapeutics company Moderna as CEO in 2011 and led its efforts to develop a commercial COVID-19 vaccine during the global pandemic in 2020. Prior to this, he held senior roles in the pharmaceutical and biotech sectors, including CEO of bioMérieux and Country Manager for Belgium at Eli Lilly.

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Transcript

[00:00:00] Intro

Stephane Bancel: I joke with people that if you told me when I discussed with Uber in the early days, that I would have to raise 5 billion, a hundred percent chance, we have not have taken the job. ’cause I would’ve been petrified. There’s not a lot of sugar coating in my family, and so I’m a bit the same. I’m an engineer, so I like facts.

If I believe it’s black, I’m not gonna tell you it’s gray or white. And we have around 10 molecules for over rare disease in a liver that will become copy and paste like we’ve done with all vaccines during the first one. It’s like building a new industry scientifically almost. But then doing the second one is almost like Chip because you just change the sequence, which is just information of Gene.

The team has already within 2000, GPTs within the company, and they are literally across everything. So we, another podcast one day. 

Philip Hemme: I will get back to you.

We have new to a new episode. I’m host Phillip, and on the show I’m entering the best Europeans in biotech to help you grow. Today I’m in Boston, more precisely in Cambridge and Kendall Square. I will talk with Stefan from Moderna. That’s the headquarter. Stefan co-founded Moderna in. 2010, raised $5 billion, helped solve the pandemic, and now the company has three products approved on the market.

I’ve known him since 2014, and he is one of my biotech heroes. We will talk about the lessons he learned from this extraordinary journey. We will also talk about what’s next for the Ling field and how AI is impacting so many parts of the company. So here’s my conversation with Stefan. And please hit the like or follow button if you’re enjoying it.

Welcome to tfa. 

Stephane Bancel: Thank you so much for having me, Philipp. It’s good to see you. 

Philip Hemme: It’s been a while. 

Stephane Bancel: Yes. 

[00:01:44] Building an effective team

Philip Hemme: So I wanna start with personal lessons. And actually one thing I quote you a lot is, and also on the show is you told me that biotech is about people, people, people as real estate about location, location, location.

So can you like Yeah. Expand a bit on this? Sure. 

Stephane Bancel: I think it goes back to the observations I’ve had building the company. As you know, there was nothing initially. And then the team worked on the science. And then when with good science, we worked on manufacturing process and then we took the drugs to a clinic, one drug, two drug for drugs.

And then the pandemic happened and we rallied the troops. And if you look about it, all those things have been done by people, obviously. And one of the thing I’ve realized is that the culture you set. The culture fit between the enterprise and the people you hire. And I think it’s really important as you hire people to make sure they fit your culture.

Every culture is different. And there’s not good or bad culture. It’s just a culture. It’s like families. I think families have different cultures and, but I think it is important is a fit. And so I think you need to make sure as a leader to really set up the culture, to reinforce culture.

You get the best people be able to work for patients. 

Philip Hemme: Yeah. And I remember one thing you told me as well was like, you preferred a team of, and b Science then a science was B team. Yes. Because the B team can can screw up the A side. Yes, 

Stephane Bancel: that’s correct. And actually I studied Bob Richard. Yes, exactly.

I was gonna say, I studied from Bob Langer in the early days of Moderna. I remember Bob. Being invited to meet some investors in Moderna. That’s obviously CSO weary. Spring of 2012, really early and one the thing Bob told me, investors I re, I forgot the question I was asked, but I remember Isly, he said early in my careers, ’cause of course he’s a scientist, Bob Langer.

Like I used to believe that the most important was to have a science. And what I’ve learned over the years, there’s only 40 plus companies, is that you better have a B team with a science versus having a b science with a team. 

Philip Hemme: Yeah, that’s good. Yeah, like that. 

[00:04:10] The Boston biotech mafia

Philip Hemme: Switching a bit, I also, one thing you told me I think was you talked about the Boston Biotech Mafia.

A bit like the PayPal, maa, I guess so in Silicon Valley, can you, ex ex I expand a bit on this, like 

Stephane Bancel: yeah, sure. Like, so for people listening who I’ve never been to Boston, you had the chance Philip to been here many times. It’s actually Cambridge. It’s actually the Cambridge Mafia. Because C queer, Maia, because exactly.

Because we’re literally on Cambridge, not on Boston side of the river. And MIT you can see from your seat is two blocks away. Because Mono now is big. It’s only us in this building. But we actually used to be in the building on behind you. 

Philip Hemme: And this one though as well. We, 

Stephane Bancel: we we’re at five or six building as we keep growing.

But we started here in this building. It’s full of small companies. Yeah. And so by definition you bump into people, you go to restaurants, you go to meetings, you see people. And so, and then people leave companies and they start another one. And so if you’ve been in this ecosystem for long enough. There’s a lot of connection, there’s a lot of friendships.

That’s I called the, the, the, the, the, the biotech mafia of Cambridge. I say Boston from when we’re very far away from Boston. ’cause most people don’t know the difference. And, and that’s sort of a uniqueness here, is that it’s easy. I’ve spoke to a lot of colleagues in California, especially in the tech world.

And the, the Silicon Valley is not the same because you have to get in. Well, literally here you can literally go down the building and just go to get a, a coffee, you at Starbucks or whatever you’re gonna make you, you, you might meet five other CEOs and two professors from MIT. Yeah. 

Philip Hemme: That’s, I mean, yeah.

What’s amazing is there’s a density, cannot stress whatever, whatever, three, four mile five miles, and they call it what the highest density of brains, 

Stephane Bancel: you know. And it’s true. If you look at all the molecules that have come, I mean Iram, you know, is two blocks away this way. There’s Bargen and one block away.

There’s ENE building. This is Agen building, and then all those startups, like it’s incredible and literally two blocks away, as we said, it’s, it’s a Koch Institute where Bober and all this team occupies the top four. And you have so much innovation there. Also, I think the academic world as well as incredible innovation, which a lot of time becomes companies 

Philip Hemme: Translate.

So you, and you’re, you’re born in France or French in the US and I heard from, from a common connection, I said, you sometimes you’re more American than French. 

Stephane Bancel: Yeah. 

Philip Hemme: How do you feel? 

Stephane Bancel: Yeah, I would, I would kind of agree. So it’s interesting. I’ve always loved business. I come from a family, we talk about culture, business culture, but I come from a family where.

We say fingers, we believe them. Or as we, there’s a lot of, you know, so sugar coating in my family. And so I’m a bit the same, which is, I say things, I’m an engineer by training, so we are all biased by own trade. And I’m an engineer, so I like facts. And so if I believe it’s black, I’m not gonna tell you it’s gray or white.

Don’t say it’s black. And if you say it’s gray or it’s black and so it’s true that when you look at American business, there’s a side of it that is. Really similar to that world where you look at facts, you make decision, you pivot quickly. But I think it’s something also required in science. I think one of the success of the culture of Moderna is the ability to pivot the strategy of a company quickly or new data.

And not to be scared to say we were wrong, because before we believe something else, data wise and science wise, and with this new findings. The previous strategy is not the best strategy, and it’ll change even if you look like a fool because you, you change strategy or what you used to say was right is actually now wrong or vice versa.

But that’s a piece where I think the focus and the obsession on the mission to help patients, if this is where you, what you care about, looking at a full a few time a week, a few time a month is fine, as long as we help patients. 

Philip Hemme: Yeah. Yeah. That’s, that’s the most important thing. And I’m curious on the, you’ve never wanted to come back to you.

I guess you travel a lot there, but like coming back or relocating to your opening? 

Stephane Bancel: Right. People ask me the question regularly. I don’t think it’s a practical question or, so I cannot give a practical answer, which is, you know, we are 5,000 people here in a mustache sets space. The company was started here because as you recall, it was a set of founders from Harvard and Bob Ger from MIT and UBA and from flagship.

So you have three academic co-founder and one kind of entrepreneur, co-founder with uba, and so everything is here. Most of the board is there. So I just don’t see a practicality where I can go to London or Paris or Berlin. It just cannot happen. 

Philip Hemme: Maybe to retire, 

Stephane Bancel: maybe to retire, but that’s a very different question that’s not for.

Philip Hemme: For today. 

[00:09:10] mRNA as a platform

Philip Hemme: Curious on the, also what one I think you, I remember you told me, I, I want to build the, the next AM Amgen or the next big biotech. How is it still like, or how is it still true? 

Stephane Bancel: So if you recall, because we have a benefit and like some of the nels to have known each other for many, many years since.

The first month of Moderna, I told all our stakeholders as we were hiring employees, hiring board members, raising money. I told everybody, I said, look, because the money is information. We’re trying to build a platform, but at the end of the day, we’re gonna have no drug. We a lot of drug. 

Philip Hemme: Mm-hmm. 

Stephane Bancel: And I used to tell everybody a long time ago, you make no scientific sense.

It would be a one or two drug company. It would be zero or a lot. So the good news, now we’ve, as we taped this discussion, we just got all, you know, another positive news from FDA overnight. If you have review approval of NextGen COVID vaccine monitor recall m next spike, which was approved by the FDA at the end of May, we have now a free BLS for different mRNAs.

They’re all very different mRNAs, different chemical entities, different sequence, and so we are already three molecules. We said we should have a flu data phase three efficacy in the summer. We’ve already shown the flu COVID combo antibody data looks amazing. Last year we’re working for CMV, working for neuro.

We showed, you know, three year survival data in cancer that I hope we can talk about that. So exciting to me. I think the next frontier modernize in oncology and so it’s not gonna be zero drug. So we know it’s gonna be a lot. So is life a strike line now? Of course during COVID we had two like our partners at BioNTech, you know, or colleagues at Bion to, to do incredible things to get the vaccines out so fast.

But now if you want to win a time of kind of really focusing the company on the key programs, the priorities, building, rebuilding, launching, managing the sales, decrease post pandemic unquote hangover, because we always knew that. I used to tell the team as we’re building the manufacturing capacity, I say one day we’ve to climb down the mountain that we’re building right now.

Because it was obvious that. You don’t need everybody to get a vaccine every year. Actually, in 2021, I got three shots because I got the first two plus a booster, and I always say people, it makes no sense that I will get three shots every year forever. Yeah. So you just do the math Plus people who don’t want them.

So, so we came down the, we’re reclaiming the Montana with free products approved. The cancer data and all, everything. So in the next few years are gonna be really exciting because I think the platform is already coming to music in the next few years because you can see model line 26, 27, I think 6, 7, 8 products approved, including infectious disease, oncology, or rare disease.

We’re now in phase three oncology, pivotal in rare disease, in in, in the pivotal studies. And so. Two years’ come really quick and in two years time we could be against seven, eight products approach. 

Philip Hemme: Yeah, that’s amazing. We’ll get back to, we’ll get back to this. Sure.

[00:12:25] The transition to entrepreneurship

Philip Hemme: I wanna talk a bit on the, a bit, I mean, a bit personal, you know, personal question, you don’t need to answer it, but on the, on your shares, you own quite a lot of shares of Moderna and obviously the stock price went off crazy.

And then, I mean, I guess you, you. Virtual networks as well. Like how, how did it feel like I mean, you also, I mean, kind of climbed the mountain, climbed down as well a bit. Like how, how did you Yeah. Perceive feel about it? Sure. So the good news 

Stephane Bancel: is I’ve never been driven by money. So for me, money is a consequence of success.

It’s on the goal. My wife and I have said publicly many times that we’re gonna give most of our money away. Which we started doing because during the pandemic we had actually my, one of my first big stock option grant on modern. I wrote a blog about it that was gonna expire. So I had to sell the shares.

I mean, I had to exercise the option. And so then we sold the shares and we gave a hundred percent of the proceed after paying our taxes to Charity. Charity. And so the yoyo of a surprise, I think only matters to people. If you care about money a lot and if you care about selling because like B Warren Buffet says the stock price is irrelevant if you’re not buying or selling.

Philip Hemme: Yeah, 

Stephane Bancel: and given I have a very long term view on this company, given as we just spoke about, we, we have free products approved a big one or we’re having seven, eight and more, and I’m not a seller, is that actually I bought stock in February. I bought quite a lot of stock with the cash I have personally because the price at which one I is in those days makes no sense.

And as you know, with stock market, there’s always figures and grid and every, you are overvalued like we were during the pandemic, or you are what I believe is undervalued right now. And so it just, years of life, I always remind the team ’cause of time. It’s, it’s disturbing to employees. ’cause everybody has a company has stock option.

I mean, at the policy since day won, the secretary is, you know, the. People working in the factory on the shop floor, everybody has as, as equity, as Moderna because I, I want everybody to behave like an owner and to share into the success of their work, which as you say is very American. And and, and sometimes I talk about it with people who say, look when the stock price was, you know, very high during the pandemic, it made no sense.

Philip Hemme: It was like higher than whatever, gsk Hundred billion market. 

Stephane Bancel: Yes. And, and so, and sometime it was crazy because I remember. There was a morph, I think it was in summer of 2 22, where the stock price doubled in a morph on no news. Like there was literally no news, no press release by the company, no new publication, like Zero News, and the stock price doubled in a morph for more than a half.

And I kept telling people, this makes no sense, but get too excited. Put your head down, do the work, do the science. And I tell ’em the same thing now that the stock is, is, is not in a good place, it’s raw which is don’t sell your share now. The, the work, the science, the stock price will catch up. Nobody should be driven, my opinion by the stock price.

We should do the right thing for patients. If we do that as a cost sequence, we’ll, we’ll, we’ll, we’ll be, make profit and that will create shareholder value 

Philip Hemme: for stock price. Yeah, that’s good. See this maybe just a, a quick question on that, on your career, because I think you, you started more. You study in France, you study in France, you worked at a lady, I think a bit in the US as well.

You went back to France, CEO, like across, like what did, I don’t know, what did you like, how, how did, basically, if you look back at it, how did all these roles lead to where you are modernize where you are now? 

Stephane Bancel: Yeah, it’s a great question. So the piece I’ve been lucky is since I was maybe 16, 17 years old.

High school always dreamed of being a CEO of a technology company. One day I don’t think I have a big ego, so I would’ve been happy by the end of my career. I would’ve run a company of 10 people. Literally I’ve been it. But the piece I wanted to do one day, and I think because it’s how my brain works.

I’m an engineer and I’m a system thinker, and I always dreamed of the idea of by being the CEO, having to make sure all the parts make sense together. You have a good science strategy, but your manufacturing strategy is not aligned with it or, and all your commercial and all your financing strategy, you’re gonna failure because all those things are linked.

And I like the fact that I had this belief that the company is basically this system. Whether the CEO has always kind of rebalance because. I will be outside environment or the scientific data or the customer performance on sales. We leave back the system and you have to rebalance the system in real time over time.

And so that was kind of the, the, the thing I, I think I wanted to do. And so I’ve always asked myself the questions for my career, say, how do you get there? And so I started after my engineering degree which I did a bit in France and a bit in the US in Minnesota. I went to Japan at. ’cause for an engineer it was, I, I wanted to be in life science.

I always thought that life science was this great industry where you use your type to make products to help other people. And I just think it’s, it’s like a super cool to be able to use your time to do good things in the world. And so as an engineer I was kind of a easier route to get into life science.

And so I learned a lot about diagnostics and then I went, got my MBA to the US when I joined UIE because I wanted to go into the treatment side of the continuum of diagnostic and then treatment. I had a great run. Lee was a great, I mean, it’s a great company, very great company. He worked for him in the uk, in the Indianapolis, US in Belgium, and then er, the chairman of B me called me and told me that they were looking for a new CEO and so they ended up giving me the job.

And so I was, you 

Philip Hemme: were quite young. 

Stephane Bancel: I was quite young. I think around 33 years old, if I remember. So so I went back to diagnostics and then the founding team of Mo of, of Moderna was looking for a CEO had one employee. And so they wanted to put money in and start building a business. And I’ve known Ian, who a chairman and was the cofounder, a co-founder of a company to about using MR as a.

He knew I’m a biochemical engineer by training, so my first reaction to him is like, you’re crazy. You gonna inject the money in people and they’re gonna make their own protein. Like bioreactor. He is like, yes. Like you’re crazy. And he is like, I don’t know, maybe I 

Philip Hemme: hear you. This discussion on the 

Stephane Bancel: bridge.

Yes. 

Philip Hemme: Look for the bridges. Okay. 

Stephane Bancel: And so all those pieces led me to Moderna because I learned the CEO job at er. I always tell people I had not, I don’t know if I would’ve been successful in this job as CEO of Moderna if I not been CEO before. 

Philip Hemme: Hmm. 

Stephane Bancel: Because it’s so hard. I tell people it’s hard. It was harder time, harder to do the CO job or the COB me job and the CB.

My job was hard. ’cause he was in a large company, 40 countries, 6,000 people publicly traded a lot of product line. It was not an easy job, but this job was 10 or hundred x harder. Because the science, there are so many unknown. ’cause no, nobody had ever done any drugs before. Raising money, had never raised money before.

And, and we raised 5 billion in the modern history. And I, I, I joke with people that if you told me when I discussed with in the early days that. I’ll have to raise 5 billion, a hundred percent chance will have not have taken the job because I would’ve been petrified. I’ve never raised a penny in my life.

I don’t know if before, actually I think no company is before, will raise 5 billion. So you have told me you have to raise 5 billion and nobody has ever done it, and I never done it myself. So I think I would’ve just freaked out and told, no worry too crazy. Find somebody else. I’m not doing this thing. So I think sometimes for entrepreneurs, I think not knowing is really important.

I had recently a podcast with Ian, CEO of Nvidia and he was asked a similar question and he said, yeah, I will not do it again with what I know now. And all the pain it has taken us and me to build this thing over the last 30 years is we journey ’cause of suddenly in 93 he is like, I will not do it again.

Is like, and we made a comment, which I we, hundred percent, which is there’s a naivety of entrepreneurs because most of entrepreneurs have never done it before. Some are several entrepreneurs, they have done it before. So maybe there’s super humans or they are maki or they are crazy or I don’t know.

So 

Philip Hemme: I was about to say, 

Stephane Bancel: yeah, yeah. But if I don’t been c there is no chance done that. And if I had not work at Lilly. There’s no chance I could have done this job. Well, we might have been bankrupt 

Philip Hemme: and looking back, you would do it again. 

Stephane Bancel: I, we do it again for only one reason, which is, and it’s the same reason that I did the first time over real time, which is it was a crazy, crazy decision.

All my friends and family told me not to do it. Except my wife, to be fair to my wife. And the way I thought about it at the end, after spending a few weeks talking to UBA and the founders, talking to a few scientists who get a bit, ’cause you know, I’m an engineer, I’m biochemical engineer, I understand a bit the space, but I not PhD in molecular biology.

And so I had to talk to a few experts and to help make my decision. And it was clear that the odds were really against us. ’cause already, as you know. Starting a company, any field is hard. Most companies fail in biotech even harder because it takes so long and you need so much money. And doing a biotech new company with a new technology was like on the borderline of insanity.

And I told my wife like, look, it has maybe, maybe 5% chance are working. And so the reason I did the first time is I did because I believe that despite the very, very low odds of being successful. If we’re being successful, to the point we started our discussion today, it was gonna be a platforming, gonna make a lot of drugs, and the mental model that I had in my head, which has served me a lot to play a long game and to try to be thoughtful about the strategy is to say, if you think about it, recombinant technology, the biotech industry.

I started in the seventies, we Amgen and Genentech, and then Biogen and a few companies. But if you look at what it has done in 50 years, ’cause now it’s 50 years after and what it has done amazing in term of new protein-based vaccine and the insulin and the K2 drug and the checkpoint. And, and, and then I could go for ours that now seven out top 10 drugs sold by pharmaceutical companies are biotech technology, product drugs.

The impact on humanity has been gigantic, and it was clear to me because of a biology, because we are at this amazing, exciting time where we’ll learn more and more about human genes and what they do and how a human body works and so on. That over time, we should be able to find ways to get the money into new cell type.

And once you’re in the cell when it’s easy, just molecular biology, it’s very logical, it’s very deterministic. And so it was clear to me again, what I told you, which is it was gonna be zero or a lot. And so the opportunity to go and try to work really hard with a lot of super smart, dedicated people to do something that could impact humanity for 5,000 deals, he’s like, I’ll sign again today.

Even now I know the pen and I that it will not be fun every day. But the journey is so worth it and the personal feeling of helping other people is such a, is such a amazing, unique feeling. ’cause the matter model I always had, and I tell my team all the time, is I think about my, the people I love in my life and my, my wife, my kids, my parents, my friends, my best friends, and so on.

And I use that mental model as two useful. People you love. There are people in your life that I’ve never met. I must probably never met them in my life, but that you care a lot about. And I always believed for the way I was raised, that I don’t love the people that I love in my life more than you love people you love in your life.

And so I always a matter mother of people I care about deeply as I want those people to be protected with vaccines. I want people to have treatment where they have cancer. A family has a lot of cancer history. And so. I’ve always used that meta model to, to think about how do we really push hard? As I know sometimes there has been a criticism of our culture, but it is what it is.

How we really push hard because every day matters. ’cause people are gonna be waiting either today or in five years time, and if we’re late by a day or week, those people, which people in their life love them, won’t have a product that we should bring to them. 

Philip Hemme: Yeah. Actually, it’s funny you mentioned the culture.

I had one thing about this year, I think you. I, I like, I like the, what you said about culture is different. It’s what’s important is the culture fit. Yes. You said the culture is a bit hard. I think you mentioned intense. 

Stephane Bancel: It’s demanding. Yeah, it’s demanding for sure. It’s, it still is. Yeah. Yeah. For, for the same reason that it was on day one, which is the mission is what drives many, if not most of us at the company that I believe deeply.

In my guts, in my brain. In my heart, that’s every really matter. I don’t want, again, I use again, my family as a mental model for everybody. I don’t want my wife not to have a cancer drug we’re working on if she has multiple myeloma in five years because we are a yell late because we don’t do our best work.

If we do our best work. I’d be able to look at myself in the mirror in the morning when I shave. So, yeah, are able, with your best work, we took the right risk. You know, we push each other to get the best idea to win, not who was the most senior person or who was here the longest, or whatever. Those type of things, I don’t care at all about.

And so that. Demanding culture is demanding on ourselves and of each other. And I’ll tell people is be demanding of me. I, I believe I’m super demanding of myself, but be demanding of me. Push me, challenge me. And I wanted this culture where the best idea wins. And I always said, new employees. I don’t care if you’re been in the building a year or 10 years, if you are technician or vice president speak up, debate the ideas.

’cause we are data driven, fact driven basically with culture. And, and you to speak up because if you don’t, again, somebody you know, maybe in five years or 10 years won’t have a drug ’cause you didn’t speak up. 

Philip Hemme: Good. So, yeah. 

[00:27:31] mRNA pionners

Philip Hemme: Transitioning a bit more to the, let’s say MA industry. And one thing, I mean, you just mentioned about the science that when you started it was crazy m and a that, that it would work.

Yes. I’m cur I mean, and I think. When you started, I mean, there’s not too much, but I think Ima, Ima was on the Shor of the founder of vac. Yeah. I think he had started a few things a few years before, or I don’t remember exactly when the, oh, actually no. 

Stephane Bancel: You what? 50,000 a lot before we started. 2000 era.

Yeah. Yeah. So a decade before we started vac. 

Philip Hemme: But he started really from zero. From Zero before Scratching the gap. We, we started from zero too. 

Stephane Bancel: People forget, but the first round of modern was a $2 million round. Yeah. So you know, much later the company’s like, when we’re in the clinic, we did very big rounds that we were known for kind of a $500 million round every 12, 18 months.

But people forget the first round was 2 million 

Philip Hemme: and the first coffee machine was called Pascal North. Yeah. I’m curious now on the science, like if you look back on, I think on, let’s say on the paper. And when you describe it, you inject the Mr. A, it produce a protein, like it’s logical. If it works, it’s, it’s amazing.

Can you say a bit more on, on what was the biggest like science hurdles Sure. That were overcoming? 

Stephane Bancel: Yeah. And there are a few that were known by everybody almost in the field that are raised touba. During that very first discussion about using mRNA as a drug is mRNA is known to be highly immunogenic. Our immune system has developed tools over fathers of years to protect against ourselves against viruses.

’cause as we all know, there’s a lot of mRNA virus. Yeah. And so usually when your body sees a foreign piece of mRNA, you think it’s a virus and it gets very upset with it. That’s how we survived as suspicious. So these, I was of course aware, so, you know, is immunogenic, like I know. And and then I told him, you know, Mr.

A is very unstable. He’s like, I know I said, okay. And so there was a lot of technical error, which is how do you stabilize the mRNA? How do you reduce the immunogenicity? So the reaction of the immune system, and then how do you get it to the right cells? I think some of the work that has been done in the labs by Rosie.

And Carrico and Wasteman and others over the years was in Petri dish. So you don’t have a delivery system, you don’t have an immune system in a Petri dish, you’re serving, you have all the sub cells from the same tissue. So it’s a very easy system, but it’s a place to start, obviously. Yeah. Need to start simple before you go complex, obviously in science.

And so we had to take this from a very simple concept to the hurdle of a very complex. Human immune system and then to get air man in the right side. To give you a sense, one day I remember, it must have been 2014, he must be three, four years old, or maybe 15 afterwards, where we had a massive issue in our rare disease program in animals.

It looked amazing in our rats. Amazing. So it was injecting IV into a rat and mRNA to go to the liver to replace the protein that in the future, a kid now a rat was missing. So that the right liver will be functioning normally like your liver and my liver. Okay, so we’re correcting a protein deficiency.

It looked amazing in rats. So we go to monkeys, it doesn’t work and we don’t know why, and we repeat it and repeat it so it doesn’t work. And then we do a lot of histology work. We look at, you know, tissues and so on, and we rise in the liver. The mRNA was coming through the, the, the, the central vein, you know, of the liver.

Then you will go into the first cells that go after the vein, which is the cap cell before getting into the next layer of cells called the hepatocyte. We didn’t need to come to hepatocyte in the market. It was stuck in the cap cell. So you go, you know, you would go IV into the, the, the vein of the body for a blood, you’ll go into a cap cell.

It was stuck in the monkey, which did not happen in the right, in the mass. So it took us a long time to first figure out what was a quorum, and then it took us even longer to figure out how to fix it. Remember you, you model to start optimizing. The technology is again, the mouse and the rat, which you already learn behaves differently than the monkey.

So it’s type of things that makes a difference between a cool scientific ID in people’s brain or in a Petri dish in the same cell system to take into a living system and to scale hip across species size, which also raised the question. Now the good news, we are sitting in 2025 and we know it works great in humans actually.

Why we’re in phase three. Because of phase one, two of the kids. Some of em have been several years on drugs have a 70, 80% reduction of hospitalization because of a drug. So it’s working. And when you hear a patient story from a parent of a quite amazing and touching stories, so that’s why now we were in the phase three, but if you get the journey of that technology, it was so hard.

The good news now, because again, AM is a platform, AM is information. We have a second one behind it, and we have around 10 molecules for over rare disease in the liver. That’s really become copy and paste like we’ve done with all vaccines, and that’s where you’re gonna see the power of the technology doing.

The first one is like building a new industry, sensically almost, but then with the second one feels almost like cheating because you just change the sequence, which is just information of a gene that’s available on the internet and you have a new drug and you write it again. 

Philip Hemme: Can, can you just go a bit deeper into the how did you, the how, how did you reduce immunogenicity?

How did you improve the stabilization? Yeah, the, how did you improve the delivery? Like, 

Stephane Bancel: so there were a few big scientific steps and there were dozens or hundreds of small. I think it’s tough to achieve all those things apart. One that is important and well known is the modification of a UIN that was initially discovered by Caro and Westman for which we took a patent from Upen years and years before the pandemic, which has, you know, got the no price of our work, which was clearly only important stepping stone of the world puzzle of how do you make mRNA work safely in human and get into the right cells.

There was a lot of manufacturing know how to learn. By doing it. Yeah. ’cause you make the mRNA and then you inject it and it’s are immunogenic and you study what is in the sample of your manufacturing product and you realize there’s a byproduct of a enzyme that create little pieces of mRNA that actually.

Excite the immune system. Okay? And so you can separate them by doing clarification and you can test them together or separate it. And you realize that when you take them out, you have less immune response and you keep at it. So there’s a lot of manufacturing r and secretly we use machine learning back in 2017, so pre COVID and pre gpt and so on with machine learning to evolve some enzyme to remove some of the issue we observed that exists in nature.

So we invented enzyme that don’t exist in nature for manufacturing in our plant. That was another part of technology. I guess. It was 

Philip Hemme: important to have your own manufacturing sites, correct. 

Stephane Bancel: There’s a lot of technology around, you know, optimization of the mRNA. As you know, there’s a lot the, the five tail UR free Pro five prime the cap at the, which kind of the nose of the mni, so there’s a lot of peace on the MNA molecule itself.

Then the formulation, which both protects the mni from degradation in the blood because mRNA just injected directly into blood is degraded in seconds. Again, for evolution, we have enzyme in our blood that will just chew up, like, you know, candies very quickly so we don’t have time to replicate and become dangerous.

And so part of the delivery system that we developed, one of the goal was to protect. Mr by putting the Mr R inside like a product layer, if that makes sense. The other part was to carry, or sorry, what? That’s, yeah, I forgot. That’s the other function of lipid is to take it to the say where you want the mRNA to have, its its biological action.

By making the protein you want in the right cells. So there’s a lot of, so that’s why if there was, again, it would be unfair to scientists, but there were some big stepping stones and dozens and dozens, again, maybe hundreds of small stepping. So, and by the way, we’re not there. 

It’s only, you know, 20 old technology.

We’re investing, you know, 200 hundred million dollar per year on basic science to keep pushing the boundaries, get their money into new organs, get into new autoimmune disease, for which we have nothing in the clinic yet. We’re still working in a lab, so we’re not done. We’re just, we still, we still getting started.

Philip Hemme: That’s amazing. 

[00:36:32] Innovation at scale

Philip Hemme: On the, I’m curious on the, on the LLP and the delivery, because that’s, I think that’s least what I hear is one of the like major challenge in whatever gene therapy or cell therapy delivery and what you said you want the MNA to go to the right cell. What I heard was LNP, that it still goes mostly to the liver, like.

Is that true? Or like, can you really modify? 

Stephane Bancel: So it depends how you build them chemically. It depends what you add around them that can bind into something in your body, like no receptor, like can put, you know, antibodies or leg on the surface or the lipid and depends how you inject it. And for example, an example that listeners to a podcast will know is when you inject mRNA as a vaccine in the muscle of your arm.

What we learned years ago. Monkey first and then confirmed in human is that when you inject it in the arm, a small percent of a mass of mRNA makes the protein in your muscle cells like around the site where you have your needle injecting it, as you would expect, but most of it drains to your lymph node, into your arm pit, into immune cells, and actually gets into your immune cells very, if you inject it like this, if you inject it IV with a.

Chemical structure of UID and certain size. ’cause the size of so is a, is another key process parameter. ’cause depending on size it goes to different places because it has to get somewhere, just get into something, if that makes sense. For the non-technology person. And so those are all tricks that we learned.

So we studied cell shape, size, balls, chemicals you know. Proteins on cell surface. So just a lot of pieces. Again, go back to your previous question. I think it would be so unfair to say it was one technology that was like a magic bullet that will not be true. 

Philip Hemme: And I guess also just from a field perspective was not just modern inventing, it was lot of academics, as you say.

You mentioned lot of academics and you mentioned bio intake. You, me, we mentioned vac. Yeah. I guess there’s innovation coming from. Of course a bit everywhere. 

Stephane Bancel: Yes, of course it happened in any industry. If you look at any industry over enough period of time, not a couple quarters, but years or sometime decades, you realize a lot of time industry was a lot of players.

I can remember the car industry when it started, there were hundreds of car companies just in the US and semi in Europe. And then now in the US I think we’re three car companies. I mean maybe four now with the start. Exactly. So you always see this phenomena and we are taping this, I think the day after BioNTech announced buying qac.

So it’s an example of exactly what happened in, in any industry, which is you start with a lot of smaller player and as time goes by, some don’t make it and disappear some get merged into other companies that are bigger. It’s a natural process of capitalism. To be able to, I mean, I just just mentioned we invest two to 400 million per year in just basic science.

This is not clinical drug. It’s basic science to keep learning about Mr. A. If you invest 10 million per year, and even if you’re twice as smart as we are, you’re gonna get less fixed, done just math. And if you compound it over five or 10 years, you’re gonna be well behind us, which is why in any industry scale does matter.

Look at it hyperscalers in tech right now with ai. With car companies ’cause you have all those fixed costs, the cost of designing the cars and so on in any industry scale matters. Which is why I think, given where Moderna is now I think most of the future of mRNA. For quite a while. It is set up, you have two big players, biotech and modern.

It will be almost impossible and on set that just kind of business history and practicality, which is the knowledge we’ve accumulated internally, the knowhow in the last 14 years of the company. We learned by having run literally thousands of animal experience by having 40 drugs in a clinic across four different technologies and so on.

The amount of things we’ve learned. Those millions 

Philip Hemme: of people I guess. Yeah. 

Stephane Bancel: And those, all those investments that we’re making in research every year. If you were to start today and I think go see a VC at I to start A-U-M-R-A company even, you must have a very, very good science or idea. Even 

Philip Hemme: neighbor will tell you.

Yeah. Even about how are you gonna catch up. Yeah. What’s what’s interesting on this as well is that, I mean there was a few other Mr. A companies, but actually not that many. No, there was, I raised this size. I mean, you always like the three main ones. You were the three main ones. 

Stephane Bancel: Yeah, there was Aris, but still, I think there still exist Aris in Germany as well.

Okay. Yeah. There was one in Belgium. I forgot the name. There was a couple in the US which were like a, which tried not exactly MRA like us, but self replicating, RNA the couple companies in China, capital Company in Australia, but they’re all tiny. They’re all, in my opinion, today’s world totally subscale.

So it’s smart people working really hard. I’m sure some of them I don’t know, but I’m sure working really hard. I’m very passionate. But again, if you look at it from a.

Rational business lands a chance of scaling from that place, including just having access to capital, even if you have the smartest people in the room. Access capital is only really hard, 

Philip Hemme: as you said, raising 5 billion. 

Stephane Bancel: Yeah, I don’t, I don’t wish it on anybody. 

Philip Hemme: And the, you, you talked a bit on, on, on the other programs, but one thing that I is also quite interesting was, was BioNTech.

That BioNTech is. Quite focused on, on oncology. Yes. And was actually before the pandemic was more oncology players. You have always, I mean, you have quite a lot in vaccine even before the pandemic. You better at the vaccine. How like, yeah. Why? Why? Why do you, I mean, why did you have this different approach?

What the different 

Stephane Bancel: It’s a very fair question, and I think to anybody who is curious about that question, I always advise them, because I get this question a lot from investors as you can imagine. Because both companies are publicly traded and I always tell the same source to investors. Say, spend 15 minutes downloading the S one, which is a legal document you file for an IPO of Moderna and downloading the S one of BioNTech.

’cause both companies went public, as you know before the pandemic. Read the S ones. You have been both cases, same management team, the same CEOs and so on. And you will see that both companies, I think you have ask to make sure that I, I I’m, I’m making the right comment about BioNTech ’cause I’m not there obviously.

And I’m the team. Obviously I think both company have gone back to their pre pandemic strategy because they, they did it for a reason. So our strategy since the day one discussion with no bar was. Because a field of biology has protein in every cell, in every disease state. There’s 22,000 genes. We should be busy for a very, very long time.

Was probably longer than our lifetime as a field to invent how to make a money medicine for people. I think BioNTech strategy since early the BioNTech confirmed in their S one document is. They want to be one of the most impactful oncology company in the world, and I believed. I’m oversimplifying again, ask a girl, but I don’t think I do it.

Disrespect. I believe they don’t really care about which technology they need to get there. Their obsession, which is very noble and are really rooting for them obviously is to have a big impact on cancer patients. And they believe that if to do the right thing, that the thing that, the thing is the right biology strategy for that, for that cancer is to go with a small molecule and a car T and an mRNA and then freeze as best freeze after bispecific.

They will develop that. And again, it’s all to their credit. I think scientifically, I believe the same thing. If you look at our partnership with Merck, we partnered with PD one antibody. Drug. Our beliefs was that we don’t need to have to own the technology to get it done. We can do through partnership.

So you see two very different strategies being put into music. Of course there is some overlap. As you know, they did a partnership with Pfizer, which again, save so many lives at the beginning of a pandemic because they already had a partnership with flu. Because again, I believe they were not very interested in infectious disease before the pandemic.

They had partnered through with Pfizer, which of course is one of the big four vaccine companies to work on mRNA vaccine for flu together. And so I believe they’re back to their strategy. And if you look at their own calls and which of course we follow as we should, they they are very, very oncology focused.

And if you look at our strategy and how we are executing it, we’re only a money focused if we, in a partnership, we go to people that have those assets. Because if we think there’s a, a scientific rationale for combinations it’s the right thing for patients. We want to try it. Of course. 

Philip Hemme: I like that.

Yeah. So you don’t feel like you’re missing some opportunities that are, let’s say, adjacent to MA or that are not using mRNA? 

Stephane Bancel: Look, I’m sure we have or we are, or we will be. But you know, one thing you have to do as a company and as a CEO is to prioritize because. There’s just so many ideas that my scientists have and so many diseases still existing, that you could go crazy doing a thousand projects at the same time, but then nothing will move because you want, you will not have enough resources and you’ll be such complex enterprise to manage.

It’ll just be so complicated that I don’t think you’d be successful if you really care about impacting patients. So I think you have to choose what you do and what you don’t do. Strategies is mostly, in my opinion, choosing what you don’t do. Then you left to what you do. And, and I think being then discipline, execution to stick to your strategy.

If things change, you can of course evolve the strategy and you should as a change in context or hypothesis. Again, it’s good science and good business, but but I think that you have to prioritize and that makes you sometimes miss opportunities which might make you update or. Refresh your strategy.

Philip Hemme: Yeah, I like that. And actually it’s also what you said was was Merck with a PD one. It’s a good good transition. 

[00:47:12] Beyond vaccines

Philip Hemme: I wanted to, it’s also a bit let’s say beyond mRNA vaccines directly of like using mRNA as delivery of antibody or, or combination with antibody as delivery of, of bispecific. I saw the deal with, you did with, with imas.

And we had a heart rate on the show, actually. Okay. And you, like, I saw some with like in vivo, crisper gene gene therapy or delivery some cell therapy using mRNA. I think, not Moderna, but some, some others, like in Vivo CAR T was, was mRNA. So how, how did you, like Yeah. How do you, you look at it?

Yeah. How do you look at it? 

Stephane Bancel: Sure. So I. I believe we’re very practical people here, which is world make medicine. And so we try to invest in technology to make different applications of our money work safely in animals first and then in human. So the vaccine the cancer product, the real disease, the lung inhaled product with cystic fibrosis, that with Vertex.

So work on technologies that we think. We can make work or that we sometimes stumble on and then make work. Yeah. Sometime you have ity in science, of course you don’t plan for everything. That would be our organic to say we, we plan for everything sometime we got lucky. And then we try to look at what’s the Venn diagram we’ve medical need at the moment and try to, and to say, to be able to get to this vision that we might end up accompanying 20 years from now with 50 drugs on the market in many therapeutic area is what’s the bridge to get there?

And if we only dream about starting to get the money in the brain to cure Alzheimer, we might be dead by now if this was a strategy on day one, because first Alzheimer is still has a lot of biology mechanism we don’t understand as a scientific community, and I still don’t know at this day, has to get the money in the brain.

And so one reason I went to vaccine early is we thought. That our technology was ready for human testing. We were always very careful and thoughtful and worried about what the, what are the things we don’t know that could hurt people as we start our first clinical studies. So we’re very, very careful to check every thing we could and then to start a very low dose.

And one of the thing that attracted us to go into the clinic first in the vaccine for infectious disease is because you don’t need to make as much protein because then your immune system is gonna see. The protein made by the mRNA and make a lot of antibodies to protect you to future infection. The dose at which we started our first clinical trial was I think like 15 or 20 microgram dose microgram, not milligram per, not per kilo, but per human, not per kilo of human, but per human.

It was very tiny. So we like most, probably, so least chance we have to hurt a person because again, we are worried given it’s a new field. Then the other piece we liked about vaccine in terms of safety for our patient is because we, we are not gonna make a human protein via mRNA in a healthy human, which is a phase one, we have no risk of creating autoimmune disease.

One of the thing I was so worried about is, let’s say you go speak a very easy protein that people know. You go with insulin as your first one, you inject healthy, you volunteer in phase one at a low dose. There’s something that happens in human that you had not seen in rats before. So it was unknowable.

This will happen. Yeah. And the immune system of those human patients in phase one that are volunteers ’cause they’re healthy, sees that protein made by the mRNA, sees this protein is weird. For whatever reason, we could not anticipate because this was OID and that person immune systemics an antibody to insulin.

Insulin and that person becomes diabetes. That would’ve been just. You know, horrible outcome that we all have felt terribly guilty about. Yeah. To have hurt people again, we had this business to try to help people. So, last thing I want, or my team wants Luis to hurt anybody. So we go into the clinic always as a very, very serious decision that we make.

It’s not like a not decision. We’re making a whole, you know, by ourselves. Say, yeah, let’s go to the clinic. And so and so, this is why as we thought about all the things at the time that were technology, we thought was. We decide to prioritize vaccine first in a clinic, let’s just, rare disease, let’s say.

Yeah. Because we’re really worried to create safety issue in healthy people that will have been terrible. Yeah. 

Philip Hemme: Okay. Okay, so basically what you’re saying as well is that the, the beyond MA vaccine is still, there’s still some that are relatively early and you will take it step by step 

Stephane Bancel: if.

We still have data next year. We said in two six we’re in phase three study for rare disease of a liver. We could have data also potentially in 26. As I mentioned, auto autoimmune disease. We’re working in a lab in animals or autoimmune disease. It could get to a clinic into the next year or two. So we’re in a lung with inhaled Mr.

A, you know, formar with vertex for cystic fibrosis. Patients that do not respond to Vertex drug today. Vertex had an amazing scientific work for patients to get drugs at work for Cy patient. ’cause before, of course, they had no hope, but the problem with their drug, because it doesn’t work for every mutation of.

The CFTR gene of those kids. There’s around 20, 30% of the kids based depend on countries and, you know, the 

Philip Hemme: CRISPR 

Stephane Bancel: therapeutics, yeah, they certify another way. But I think, again, the CRISPR angle what I think over time CRISPR will be an amazing technology, I wouldn’t bet against human ingenuity. Yeah.

I think it has a lot of safety question marks as it should, because as you go, DNA as we know today. Cancer is always a disease of DNA. I will want, look how paranoid I wasn’t sad, I mean, worried I was about getting into a human with a R that is destroyed after 48 hours in your body on the very dose of vaccine that doesn’t touch your DNA compared to going and cutting your DNA forever.

Philip Hemme: Yeah. 

[00:53:38] AI everywhere

Philip Hemme: I think one last. Last question before some like quick fire. Yeah. You, you mentioned that you’re already using machine learning in 2017. Yeah. And you did a big deal with, or big deal with, with open ai. I dunno how big the deal was, but at least Yeah. It’s a collabor area. Can you talk a bit more on like Yeah.

How do you use AI for since 2017, for m and a specifically and in drug developer? 

Stephane Bancel: So we need another podcast for your question. Because really tri the answer is everywhere. So we, using science, we invent new molecule, like the example I shared of a protein before. We use it in manufacturing to improve process yield.

To help us do root cause investigation of deviation in the plant to help us review and approve lots of product. We’re using clinical trial, like picking the doors for phase three. We, we build the GPT I mean the clinical team build the GPT to help us to pick the doors. We use it in pharmaco to analyze the complaints getting, you know, when people in clinical trial or.

In the real world have complaints about the product that might be or not be product related. We use it in commercial for marketing. We use it in hr, we use it in legal for contracting. We use it in finance. So that’s, I’m saying we can spend time in any one you want. We have already, the team has already within 2000 GPTs within the company and they are literally across everything.

So we have a podcast. Yeah.

Philip Hemme: I’ll get back to you. 

[00:55:16] Quickfire

Philip Hemme: Well, quick, quick fire. Just a few quick questions if you can on like, yeah. Yes. No. One sentence. What’s on top of your mind at the moment? 

Stephane Bancel: How do we scale the company to go back to profitability in the next couple years? To Redel deliver on the mission? 

Philip Hemme: What’s the most d most difficult decision you had to make as cu in the last two years?

Stephane Bancel: Is to reduce the footprint of a company because of the demand of products was coming down. So we had to

Philip Hemme: One advice to young life science professionals who want to be in your shoes. 

Stephane Bancel: So if my shoes mean, CEO is learn about the science. If you’re a scientist, learn about leading people because it’s about people, people, people, and learn about. I’ll be curious about financial markets, vc, ’cause you’re gonna have to raise a lot of money.

5 billion. Not necessarily 5 billion, but LAB platform. Moderna. 

Philip Hemme: What’s your favorite biotech or science book? 

Stephane Bancel: Hmm. I love to go back to old rep pastor books. So I’m reading right now all rep pastoral book is one of my hobby. I’m buying them in all bookstores for 20 bucks. Get originals and so on.

And just to go back and see the amazing curiosity that he had, he revolutionized four scientific fields in his life. Just amazing. 

Philip Hemme: I will, I will check it out. One, one last one, one last one. One mistake you made in the past 12 months. 

Stephane Bancel: Oh boy. How long do you have? Because I made one mistake. I need to think about one.

I made people decision, mistake. I made them all my career. ’cause go back to where we started with the, the question of it. So, yeah, I met people decision mistakes in the last year. 

Philip Hemme: The la last one More positive, but one, one new habit you adopted recently. 

Stephane Bancel: It’s around using GPT. I deleted my Google search.

For my browser, I put the bottom of my iPhone, the charge GPT app. I mean, we have GPT enterprise of course, for security reason and, and all data is to start to always ask myself a question before I do something like sending an email to somebody, asking for an analysis or whatever is gonna do it by myself with GPT and are using deep research 

Philip Hemme: elective.

Great. Thanks, Stefan. Thank you so much, 

Stephane Bancel: Philippe. It was great to see you again. Thanks.

Philip Hemme: I’m impressed by how Stefan and the Moderna team were able to deliver on the trip. I’m also impressed by Stefan’s humility and openness. If you also enjoyed this episode, please had the like. Follow a review button. Any of these actions would help a lot the show to get to more people. If you want to support the show even more, you can make a donation via the PayPal link below.

If you wanna see similar videos, please check out our YouTube channel where we have many more. Also, I would be curious to hear what you think. So if you could leave a comment wherever you are or shoot me an email@philipatflo.bio. Alright, thanks for watching to the end and see you in the next episode.

 

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