I apologize.

So why do some people believe over time, again, not next week, over time it could be bigger than K2 drug? First, because we believe it's going to work everywhere where K2 drug works.

But then also another piece that we believe, with Merck and Moderna, is if you go early in disease, like stage 1 disease, there might be a very interesting use of intismeron as a monotherapy, meaning by itself, without cathedra.

And we announced in the spring that we have started a phase 3 clinical study, so a big 1,000-people study.

on patients with stage 1 disease in lung cancer.

Because today, if you have lung cancer diagnosed in stage 1, which you can do with a CT scan, especially to former smokers, the standard of care is surgery and monitoring.

Why are checkpoint medicine like Ketudra and others not used early in disease? Because of the lifelong side effect profile.

And final question, Stefan, I want to ask you, why should investors buy Moderna stock now? And what is the TAM? How big an opportunity, how big could this company be? And also, can you address the competitive moat that your company has? Why can't some other company do what you're doing, for instance?

How much confidence do you have that we will start to also see efficacy and commercial availability for kidney or bladder cancers and other types of cancers?

So, of course, we're going to have to run the studies.

We believe that it's going to work in more cancers than melanoma because of a mechanism of action.

It is very different from our immunotherapy work, like Ketudra.

Those drugs work basically by helping the T cells that are exhausted.

because of your cancer.

Our approach is very different.

But when you look back to 2015, 2016, when there was a lot of skepticism about this, what is the message here in 2026 that you give some of those skeptics today?

Talk about diversity in your organization and the culture that you're building and how do you achieve this vision?

So there are a few things.

I think the first thing is really people.

I mean, business is about people, people, people.

You get great people, you get a great business.

You get average people, you get an average business at best.

You get bad people, you get an awful business.

So Phoebe is actually wondering, what's the reasoning behind the business model of having multiple ventures?

That's not gonna be worth it"?

So you basically, you handicap for those programs.

You handicap what is the regulatory risk on top of, let's say, the drug risk or the marketing risk.

So you have to think about it.

Say, if we had this drug, we phase III positive data, let's say in two years after you do your clinical study.

What is the probability that we go into a regulatory complex situation? The thing that has been really encouraging, and you have seen it what happened with flu as you describe, which is the working team at the FDAs have stayed very focused on the science and the data.

And I think what happened with the flu program of Moderna this year is a good example of that, which is we started to review a file.

But I, I, I started with quickly because that's what I feel like I've heard most about, is that it just simply can move so much faster and do computations and, and, and make predictions that would take humans a, you know, a, uh, a, such a different amount of time to, to do on their own that it's not even comparable.

That's not gonna be worth it"?

So you basically, you handicap for those programs.

You handicap what is the regulatory risk on top of, let's say, the drug risk or the marketing risk.

So you have to think about it.

Say, if we had this drug, we phase III positive data, let's say in two years after you do your clinical study.

What is the probability that we go into a regulatory complex situation? The thing that has been really encouraging, and you have seen it what happened with flu, as you describe, which is the working team at the FDAs have stayed very focused on the science and the data.

And I think what happened with the flu program of Moderna this year is a good example of that, which is we started to review a file.

But I, I, I started with quickly because that's what I feel like I've heard most about, is that it just simply can move so much faster and do computations and, and, and make predictions that would take humans a, you know, uh, uh, such a different amount of time to, to do on their own that it's not even comparable.

On the technology

of mRNA side, what we have known and published, actually with Karolinska, as you know, the institute in Sweden that gave the Nobel Prize for Medicine back in 2015, is that with all technology, I cannot speak about all the mRNA companies that have different mRNAs, different lipids and so on, but with all technology, when we inject our mRNA in a muscle, whether it's a COVID shot or flu shot or this cancer treatment, basically the mRNA goes down to your lymph node and enters the APCs, the antigen-presenting cells, which, as you know, are key components of your immune cells.

And the mRNA gets inside the APCs.

This we've demonstrated and proven at the time of Karolinska.

And then it basically translates the message contained in the mRNA inside the APCs, inside your immune cells, and presents it from within.

So we think it's a very important differentiation from most of the previous vaccine in cancer in the field that were made by protein or peptide that basically are made in reactors, are injected in the patient, but they basically turn into the blood because, as you know, recombinant or protein, when you inject them, they just go into your blood and they turn around.

So your immune system sees them, but not in the same manner from within.

How do you think about essentially the vein-to-vein time? Like what needs to be true from the moment you, you know, sort of see a patient and get access to the tumor to the moment that patient receives their personalized vaccine?

So why don't I hand it over to you and tell us what have you announced, what have you seen in this phase three trial? And then I do want to dig in into what Moderna is doing in cancer.

Wonderful.

So Jorge, thank you so much for having us back.

We're very happy to be with you.

So indeed, last week now, we shared the news with our colleagues at Merck that after working ten years on a individualized treatment against cancer using mRNA technology, that the phase three was positive.

It's a first of many.

It's a f-first time that there is an agent in melanoma that is better than Keytruda alone, so it's a big deal for patients, of course, with melanoma.

Mm-hmm.

I remember talking to you, yeah.

Um, it's a big moment for medicine, big moment for patients.

Uh, we believe that this is just a first step for INTIS MEHR and plus KEYTRUDA.

We're excited what it is gonna mean for patients.

Already just hearing stories from patients in clinical studies has been really, uh, heartening.

And so I'm very thankful for the team that I work on this for 10 years.

That's the type of things we're trying to do at Moderna, is take very big scientific clinical bets.

Mm-hmm

Yep.

And they were monitoring the situation.

They clearly were aware already before, uh, the news [laughs] report of Wall Street Journal was aware, uh, and they were monitoring.

And when the sequence, the genetic instruction of the virus was put online in early January, we started to prepare a product to put a clinical trial because I thought, like everybody at the time, it was gonna be like SARS or MERS or a local outbreak, and then it will go away.

But I wanted to prove to ourselves, to myself and to Tony Fauci, that we could go in a clinic i- in 60 days, which was what I told him before in 2019, that he didn't believe me, could be done because when SARS happened, it took the NIH, Tony had told me, twenty months to go to the clinic.

Yep

... doing things in parallel so you don't do them one after the other," which is what people do usually to manage business risk, financing risk, where they do things one after the other once they know things are working, uh, because if not, they will be, uh, irresponsible financially in normal times.

But in war times, when you fight a virus and people are dying and economies are stopped, the government basically just threw money at the company to say, "Everything you can do in parallel, do in parallel," which is what we did.

So tell us about those results and what we should expect to see from the Phase III based on these Phase II results.

Well, good afternoon, and thank you so much for having us.

So indeed, this morning, we presented very exciting data for five year of our Phase II study.

I remind you it is a, a randomized study against Keytruda, the standard of care.

And what is exciting this morning is we showed that at five years the hazard ratio of the improvement versus Keytruda is the same when at three years.

So there's duration of efficacy, which of course is great news for patient.

And because as time has gone by, the P value of a statistical power of a analysis is actually stronger than it was at, uh, three years.

And how widely used do you think that this, uh, this approach could be, whether not just outside of melanoma, but do you think it'll only be in the adjuvant setting? Like, how big of a drug could this become?

So what does that mean for something like a cancer treatment going forward?

forward?If you think about cancer, what we know today is that cancer is basically an instability of your DNA, either caused by a genetic, you know, mutation or caused by a virus, think about hepatitis leading to liver cancer, uh, or caused by an external factor.

Think about sun driving exposure into your DNA of your skin and driving, uh, melanoma skin cancer.

So basically, cancer is instability of DNA, of human DNA.

And if you are healthy, you, you have instability all the time.

Think about the number of cells you have in your body, the number of exposure you have.

We all have instability around all our lives.

Talk a little bit about Moderna, Moderna's role in this kind of evolution of the biotech life sciences space.

Can you take us through what you did and how it changed all your plans? Sure.

I spent all my career working in infectious disease.

And so I always have an eye to new virus emerging, new bacteria emerging.

And so between Christmas and New Year 2019, as I was reading the Wall Street Journal, I heard about COVID.

new cases of pneumonia-like symptoms to people in China.

And so I reached out to the NIH asking, hey, this new thing in China, what is it? And after a few days, we realized it was a virus.

It was not flu.

How did you cope with that stress? What did it do to you?