“So the traditional approach has protein floating around your cells. An mRNA vaccine approach has the cells themselves in your own body making the vaccine.
What’s more alarming: a stranger prowling the neighborhood, or somebody who’s just broke into your ground-floor, and tripped the alarm?
That’s what happens with an mRNA vaccine. You’re tripped the alarm wire and now the cell is dialing 9-1-1. It’s calling the police at the same time as it’s making the protein and saying, ‘that’s the bad guy’.
That’s how an mRNA works. And for the last several years we’ve shown this actually works in a whole multitude of animal models. Earlier this year we published the first actual study in people. And it actually works in people.
We took a group of volunteers and injected them with a messenger RNA vaccine against a variant of flu/influenza. And all of these volunteers got the immune response we were hoping to see. The side-effect profile was pretty benign, what you would see with any normal type vaccine.
So we’ve proven the principle, this actually can work. It works in people and now we’re going to be developing a whole slew of vaccines against diseases for which we don’t have one. So that’s infectious disease.
Now for the second example, let’s talk for a minute about cancer. Horrible disease. Cancer has affected the lives of many of us and will affect the lives of many more of us as we age.
The problem with cancer at the cellular level is that the DNA is screwed up. You’ve got these mutation on this screwed up DNA, leads up to screwed up information that makes screwed up protein. And so the cell loses control.
Now, how do you figure out what is actually screwed up? Well, you got to figure out the whole sequence, right?
It took us decades and billions of dollars to sequence the human genome, and we’ve done that. We achieved that in 2003. And now we’re less than 15 years later, and it takes us a week. And we can do it for every patient. So now we can go and figure out what exactly is screwed up in a patient, and we can use that information to make a vaccine.
We take that information, say a patient with lung cancer, and we take it – we take the biopsy, we figure out the sequence, we figure out their immune system, we – and that all becomes information. It goes up in the cloud into a bioinformatic algorithm and then automatically makes a vaccine that we administer into their normal tissue; into the muscle to try and wake up their immune system.
Now the challenge, of course, is that every person’s cancer is different. Mutation happened by random chance. And so to do this you have to make it personalized.
So this is me, but if every patient is different, what we’re going to have to do is make a personalized cancer vaccine for every patient. And that’s exactly what we’ve started to do. Every patient gets a vaccine that’s based on the sequence and their own tumor.
So when we started to do this a couple years ago, my CEO stopped by one evening and said, “Tal, I get the idea but is this going to work?” And I said, “Look, Stefan. I don’t know, but we’ve got all the pieces to try and answer the question so we should try.”
And today I can tell you that I still don’t know if it’s going to work. But I know we’re able to actually run the experiment. Earlier this week the first patient was treated with a personalized cancer vaccine we made just for her.
So in the months and years to come we will know the answer of whether we can actually wake the immune system against somebody’s cancer with a personalized cancer vaccine so stay tuned.
I’m gonna finish with a third example of something called “methylmalonic acidemia” or MMA for short. Now the name doesn’t matter. Okay? This is just a disease that is caused by an enzyme that’s critical for metabolism. And children are born and they lack this one crucial gene. And so their body is not able really to fight infection properly or anytime they have any sort of stress, their body goes into crisis. They have one gene that’s gone awry and it causes a really significant disease.
If you look at what happens over time, for these children, about 1/3 of them don’t make it to the age of 10. You see here the survival curve whether the gene is completely lost or whether there’s just an aberration in it, the survival is impaired.
And, what do we do? Well there’s not much you can do because the missing protein is actually missing inside their cells. So what do we do? Well, here’s what we do. We take out their liver and we transplant the liver from a donor that is healthy and normal into these kids.
Think about it. They’re missing one critical piece of information and what we do is transplant an entire organ. Well, it fixes the problem, but what if there’s a better way? What if we could fix the missing information?
So based on innovations, nanomedicine, a new class of invention that Bob Langer across the river at MIT in Cambridge has been inventing, we’re now able to package this information and messenger RNA with a goal of giving it as an infusion, and then having it go to the liver to replace that missing information.
Is this going to work? Well we know the biology works. So together with the National Institutes of Health, we’ve studied this in a mouse model and this mouse has been engineered to have the exact same problem that the kids have. They’re lacking the one – the same gene. And you can see in the red line what happens to these mice when they’re born. Pretty much immediately they die. They cannot cope with stress. But if you inject messenger RNA that codes for the one missing protein that replaces that information, these mice, all of them survive, as you can see in the green line. And if you look at them they not only survive, they’re actually growing, they’re gaining weight, they look like they’re healthy littermates.
We’re hoping to start the clinical trial in the near future and the idea is the same thing here. If you think about what it is we’re trying to do, we’ve taken information and our understanding of that information and how that information is transmitted in a cell, and we’ve taken our understanding of medicine and how to make drugs and we’re fusing the two. We think of it as information therapy.
I started by telling you about Jonathan and 30 years ago, and I was a nurse in the intensive care unit, I worked two night shifts, and Jonathan came in when he was about 12 months old and very quickly became dependent on a ventilator. And for the next 15 months or so, every time I came into the unit he was my patient to care for. You know, bathe, feed, treat, play with – he couldn’t talk, he was on a ventilator, but he was very much alive and you could tell – you could play with him, his eyes would – would follow me. After a while he would recognize me. Until one day I came into the unit for my shift and he was no longer there. He had died because of an infection in between shifts.
Imagine a world where we cannot just diagnose, but we can actually use the information to create vaccines to wake up the immune system to something like cancer and to fix the missing information for children with diseases like Jonathan, so that they can leave the ICU and live a healthy life.
Thank you.”