Breakthrough: The Future of mRNA

erz Lam, Too, Duchy and war Shachen. There the husband and wife duo behind BioNTech, Weiser's partner for the COVID vaccine, and they're on their way out of a meeting with the company's chairman, Helmett yuggla ertz Lam and Uer say hello politely and then head out the door. Helmett is waiting upstairs to talk to me about BioNTech and it's race to develop a messenger RNA vaccine. Helmett laughs when I asked what they talked about that day. Next generation

m R and A treatments are in everyone's mind. Next generation now next generation No, of course, we have to think about how we developed the company because of the situation now. Helmont has known the BioNTech founders since two thousand seven. He was working then for the strong One Brothers, the German billionaires who helped fund the company. He's been involved with Biontic since the beginning and chairman of the

board since two thousand eight. When we talked, it had been almost a year since Helmot, Uger, and utz Lum found out that the bet on BioNTech and a messenger RNA technology had paid off in the biggest possible way. Helmote compares it to a moon landing. You plan and you work and you prepare, and it's all THEO nicole until you step out the door of your spacecraft and suddenly you're there. It's almost hard to believe that you've

actually made it. He tells me that after he heard the news from Ugre about how well the vaccine worked in a patient trial, he left his phone at home and went out for a walk. He lives out in the country, and it was a peaceful night. He says. He figured it would be his last quiet night for a while. That's exactly why I want to enjoy this moment quietly myself. Helmont turned out to be right. The vaccine isn't just one of human kind's best weapons so

far against the COVID pandemic. It's also the vindication for an entirely new field of medicine. Suddenly, messenger RNA vaccines are the world's best selling drugs, and suddenly the young biotechs that developed them, Germany's BioNTech and modern of from the US, are among the world's most closely scrutinized drug makers. Everybody wants to know what their next step will be.

Welcome to the eighth episode of our series. This time we're looking at what's next for the biggest scientific breakthrough to emerge out of the COVID pandemic, Messenger RNA vaccines. Up until last year, it wasn't even clear that they'd

work at all. Now everyone from hospitals and drug makers to Wall Street are waiting to see where else they can be used and what the payoff could be for patients and for the company's The technology could help engineer a better flu shop, for example, but its potential goes far beyond zapping viruses. Messenger RNA is being tested in cancer medicines and in heart disease. Some researchers are also studying whether it could be useful against autoimmune diseases like

multiple sclerosis, or even treat genetic illnesses like sickle cell anemia. UH. Some argue that we can't even imagine how widely this technology will eventually be used, and then eventually there won't even be such a thing as an m R and a vaccine company. That the technology will become so widespread that it's just another piece of the puzzle for drugmakers working in all sorts of fields. My name is Naomi Kraski and I'm a health reporter for Blue Broke News

from the Prognosis podcast. This is Breakthrough. That's the sound of equipment at BioNTech's headquarters in Minz, Germany. It's about a half hour drive west of the Frankfurt airport. Okay, what do you see here? Inside? The lab and infrastructure director frescois Perrino is showing me around. I've been at BioNTech offices before, in late and I'm struck by what

has changed and what has stayed the same. Now they have a fence and a security officer who takes his time letting me in, but the building itself doesn't look any fancier than it did before. Most farmer headquarters that I've visited have a certain class. Eveneer there tends to be a lot of modern art soaring atriums and high tech elevators. Not by on Tech. We mostly take the stairs, which is okay because the building is only a couple of stories tall. The labs are on the same floor

as the CEO's office. They've been adding research space and equipment though, so this is a kind of workbench where all the stereo processes are performed, kind of The whole facility is called cell Culture facility, and within this facility we do all our experiments with south sets from human For example, when for us while joined by on Tech, in about five fifty people worked at the Mind's headquarters.

Now it's about three times as many, and most of the development of the car Are Community Vaccine was performed inside police facilities over here. The wholesale culture facility is approximately about four d square meters and it's just about psyculturing. We're there in the late afternoon, so the labs have emptied out quite a bit. A few scientists linger taking advantage of the quiet to finished projects. Some of the people we meet are working on research that's still far

from being ready to be tested in patients. The mind's facility also makes R and A for use in research and development. BioNTech is pouring its COVID vaccine profits into its pipeline of new experimental medicines. Company scientists are working on some infectious disease projects, including vaccines from malaria, HIV, and tuberculosis. None of those are far enough along to be tested in humans, though the more advanced part of

the pipeline is almost entirely potential cancer treatments. The companies running nineteen patient trials and cancer About half of these are m R and A vaccines. In fact, before the COVID pandemic, BioNTech was basically a cancer company. As we learned in last week's episode. It didn't work on infectious disease vaccines until mid when its signed a deal with Fisser to develop a flu shot, but it's already treated about six hudd patients and cancer trials. Most were small

studies designed to look at safety. That's how drug development works. First, you test a potential medicine and only a few people, and if it's shown to be safe, you can move on to testing its efficacy in a bigger it. You might see some hints of an impact against disease in phase one, but that's not really what those trials are designed to find out. But thanks to the COVID vaccine cash, BioNTech has been able to move quickly on the bigger studies it will need to push its cancer programs forward.

One of those programs is called Ionest. Essentially, it's a personalized m R and a cancer vaccine. We're standing in front of a washing machine sized piece of equipment in one of the labs. It's crucial to the project and this machine is uh, yeah, it's very important. It's very important for us because this is one of, let's say, kind of the heart for our analysis for the Ionest treatment. In order to make a personalized cancer vaccine, BioNTech has

to sequence the genetic code of each patient's tumor. The researchers use this machine to do the sequencing. So every every the tumor is caused by different mutations inside the genome, and we have to have a look at the TOLO genome to be sure that we if we find or that we that we identify the mutations and that we know how to shape the m RNA computer algorithm helps them find the special pattern of mutations that's unique to

the tumor not found elsewhere in the body. Then bion text teams can take that pattern and build a template for an m r and A treatment. Remember how the m r and A vaccine for COVID works. It delivers instructions for cells to make the spike protein of the stars copy two virus that jolts the immune system into action, so if it encounters the real virus, it can act quickly to stop it. The m RNA cancer vaccine would train the body's immune system too, but to attack a tumor,

not a virus. It's a treatment, not a preventative measure, and the mr and A is, let's say, the needed trigger for your immune system. Bion Tech already has some promising results with Ainest in a small trial with just thirteen patients. It's now testing the technology and bigger studies and melanoma and colorectal cancer. Like for the COVID vaccine, they're working with an experienced partner. It's one of the biggest cancer drugmakers in the world, a Swiss company called

Roche Holding. You may have heard of Roche's u S unit called Genentech. I wanted to get Roche's view on m R and A cancer vaccines, so I called Charlie Fuchs, who runs their oncology and hematology product development. He's the former director of Yale Cancer Center and as an oncologist, he helped run huge clinical trials for other successful cancer immunotherapies. Charlie says the COVID vaccine's success is a good sign for the likelihood of m R and A technology working

for cancer too. Seeing that on a population level and seeing the validation in patients that this technology really does enable a robust immune responses, I think is an important step in believing that we can leverage this technology for cancer. Still, just because MR and A vaccines worked against COVID doesn't mean they'll stop tumors. You know, Viruses are tiny little packages of limited genetic code that can create havoc by interfering with functions the normal functions of a human cell,

or for that matter, creating an immune response. That's harmful, but um they're very limited. Cancers are a lot more complex.

They're a lot better at defending themselves. Cancers are human cells that have mutated to leverage the full extent of the machinery and genetic code of a complex human cell, such that it will um become a lignan spread and because it has the availability of the entire human genome associated with it, that it can actually come up with lots of different mechanisms to overcome response to cancer therapy,

to sustain itself, to avoid the immune surveillance. This is one reason that doctors often combine cancer therapies, and that's one reason, unfortunately, the cancer treatments sometimes stop helping after a few months or years, and so there's just a lot more to deal with when you're developing a cancer therapy as opposed to a virus, which is a tiny little compartment of very limited genetic code, very limited DNA r n A. Charlie tells me he thinks they'll have a better sense of how well m r n A

vaccines can help with cancer treatment within the next two years. Thinking about Charlie's words, when I talk with BioNTech chief medical officer, it's them too, Rechi a few weeks later. She and her husband, Ushahi, and the CEO are also oncologists. They treated patients for years before they started BioNTech. We spent most of our time at the patient's bedside. That was the motivation to provide better medicines for those patients whom we had to tell that we had nothing to

offer him. Some agrees that cancer is a tougher target than COVID for the immune system Sara's COVIE two is foreign cancer as part of us. So it's not about a about preventing, it's about melting away a substantial to more burden. So there are already immune suppressive mechanisms where cancer has installed, and you have to to fight against them and fight against immune tolerance because it's not really a foreign protein which you are using as target and

um so this is a very different, higher challenge. All those years working to optimize mRNA technology for cancer vaccines helped when it came time to make the COVID chat. I think the reason why we have been successful for in COVID nineteen is that we have sharpened our weapons against cancer with all those um yeah, higher thresholds for for success. And once they'd optimized mRNA for cancer, Reson tells me, they started realizing there would be potential and

lots of other diseases too. They want to develop mRNA treatments for autoimmune diseases illnesses in which the body attacks itself. Multiple sclerosis is one example for a disease like MS and mr and A vaccine will work in the opposite way how it's used against cancer or covids. Some explains.

We have shown that while for cancer or infects disease vaccines, the mrn A is used to deliver two signals or messages, namely, on the one hand, to present the target, for example the COVID nineteen spike protein or a tumor integen plus, to provide um the message that the immune system needs to attack, in particular that the c D eight killer T cells need to be directed against this the target.

For autoimmune diseases, m RNA vaccine would still wave a flag for the immune system to recognize something, but the second message we deliver is that the immune system, once it cease this target, needs to calm down and needs to accept this target and not a tack, so it's telling the body to stop turning against itself. BioNTech has had a successful experiment in this area with mice, but there's still quite a ways a way from having an

mr ANDA vaccine to test in people with autoimmune diseases. Moderna, the other mRNA code vaccine maker, is also working on an autoimmune disease project. Moderna is also working on mRNA based cancer vaccines andicistic fibrosis treatment, as well as the treatment for heart disease, and it has a broad palette of other potential mRNA vaccines for infectious diseases, everything from

zeka and FLEW to HIV. I caught up with one of the early investors in BioNTech, a German venture capitalist, in Matthias Cromeyer, at a conference in Berlin to find out more about the broader field. And you need to keep in mind that m RNA is at the center of any biological process. I mean, any gene that gets expressed is expressed via m RNA. Matthias's firm, MiG Capital, gave BioNTech about fifteen million dollars in seed money in

two thousand eight. It was migg's best investment ever. Now, he says the approach could be useful in any kind of genetic disorder where the body doesn't make something that it should, from diabetes to hemophilia or rare diseases. But the first chance to see the proof of the pudding will be the cancer trials oncology. It's definitely oncology because this is where the company's are most advanced. So I would expect for approvals um provided that these these studies

work out nicely. First approvals in twenty four or twenty five. That's a lot longer than it took to get the COVID vaccines approved. But in drug development terms, it's actually pretty fast. It just takes longer to see whether an experimental treatment can help cancer patients then it does to see whether a vaccine can stop a virus from making people sick. First of all, you can't recruit twenty cancer

patients in in a couple of weeks time. Secondly, the endpoint in in in the COVID are In the COVID nineteen um immune immunized population, it took only weeks to reach the endpoint um of a number of events in oncologies usually years that you need to wait until people have survived or not. So this is why it takes longer. It's not because people weren't working as diligently as into COVID lntine vaccination areas. If you talk to some of the early pioneers in m r and A, sky is

the limit for what else the technology could do. Remember Derek Rossi, the Harvard stem cell scientists who did important early experiments with m RNA and founded Materna. He says his original vision for the company wasn't vaccines at all. Vaccines have been in production for you know, you know, a hundred years, and they work. Uh and uh so why reinvent the wheel? Well there's turns out, as we

now know, there is good reasons for that. It's a faster technology, it's a more precise technology, it's a better technology for vaccination, It's true. But what I imagined was application towards genetic disease. Derek tells me there are six thousand genetic diseases. He says that six thousand mutations in DNA, which leads to bad mr and A, which leads to a problem with the protein, leads to disease. Derek's idea was to use mr and A vaccines to spur cells

to make the right proteins instead. Wherever protein is needed, it can be applied. So um, that could be six thousand genetic diseases. Uh. Oncology, cancer, mutated genes. Projects to study how MR and A therapy can be used to treat genetic disease are also in the works. In fact, Drew Wiseman, the University of Pennsylvania professor who worked with Catalan Kerry Co to answer vital early questions around m R and A research, is now working on an m R and A vaccine for sickle cell anemia, one of

the most common genetic disorders. The Bill and Melinda Gates Foundation is sponsoring the research. Drew tells me some two thousand people are born every year with sickle cell disease, most of them in Sub Saharan Africa. There's a here, but it's way too expensive for a lot of these patients. And what they do is they take a patient, they take out a lot of bone marrow, they infect the bone marrow with a lenty virus, and then they give it back. That's probably a half a million dollar per

person costs for for a cycle cell cure. You can't do two hundred bone marrow biopsies in Sub Saharan Africa. So Drew's lab has figured out how to target bone marrow stem cells with an m R and A treatment. It inserts a new gene into the genome of the stem cells. Instead of removing a patient's bone marrow, doctors would simply need to give them an IVY injection. To me that that changes the world, because now you can do gene therapy with a simple injection. We should make

this clear. Program isn't in human trials yet. It's being tested now in mice. As Drew has told us several times, success in mice doesn't necessarily translate to humans. Drew's lab has a laundry list of other projects as well. He's working with BioNTech on a range of infectious disease vaccines, and he's working on a pan coronavirus vaccine with Duke University, the University of North Carolina, and the National Institutes of Health.

That's a shot that could work against all types of coronavirus, is not just stars Kobe two. The idea would be to have a vaccine that could cover whatever variant pops up in the future, maybe even something that's ready to go for the next pandemic. And they're working on an MR and a vaccine against HIV. If it succeeds, that would be transformative to HIV. The virus that causes AIDS has alluded vaccine efforts for decades. It mutates so quickly,

the way it infects cells is very different. It forms a long, live, latent reservoir that's hard to get rid of um, and it has so many ways of avoiding immune responses. Again, the HIV vaccine is a long way from completion. Juice Team is also working with Duke and ni H on this project. He says it's due to start human trials next year. HIV is a much more difficult virus, so that that's going to take a lot

more work to get it to work correctly. None of these new MR and A vaccines and treatments will have the same speedy trajectory as the COVID vaccine last year. That's partly because the circumstances are so different. As we saw in last week's episode, the pandemic was in some ways the perfect use case for MR and A vaccine. The vaccine makers could draw on years of prior work from virologists on what would be the best bit of a coronavirus to use for a vaccine. They could run

relatively quick patient trials. With COVID circulating around the globe. There was no shortage of scope for testing the vaccine, and the stars Cove two virus is a lot more straightforward than cancer or HIV. Now, the companies that raced to get COVID vaccines on the market are going to need to start playing a more complicated game. They'll need to reassure investors that their billions and revenues won't just be a one off. They're grappling with a tremendous pace

of growth. Moderna in particular, has struggled to set up a global distribution network without a big partner like Visor. It recently said it wouldn't be able to ship as many COVID vaccine doses as expected this year. Meanwhile, smaller startups around the world are also working on m R and A vaccines and treatments. When I asked Helmet Juggla, the BioNTech chairman, about the biggest challenges ahead, he says

the company has to be careful to stay focused. We just need to be careful that we don't go after too many things at once, and we really need to rule Lan's work focus. Um Helmett says he thinks bion Tech will have more MR and A products on the market in a few years. It reminds me of the song by the Hungarian rock singer who appeared on that radio interview with Catle and Currico, the pioneering MR and A researcher in Budapest. We played some of it in

episode six. The song is about how you need to work hard and stay the course to achieve your goals. The diamonds and gold have a nice shine, but you have to dig deep to get it. Catalan says her favorite part of the song is about what happens when you finally hit your target. The lyrics roughly translated from Hungarian are but when you reach your goal and could be happy, you're already thinking about a new plan, already

embarking on a new road, and that's the beauty of life. BioNTech, MODERNA and their competitors have new plans too, and it's all about m R and A. Next week on Breakthrough, we'll talk with the public health leaders and scientists who are preparing for the next pandemic. Even before this one is over. COVID has shown us health vulnerable or health systems really are? Will we be ready when the next

pandemic comes? They are a very moder threat that emerges from the way we have organized our societies, and they represent a critical threat for the century. This episode of Prognosis Breakthrough was written and reported by me Naomi Krasky So for Fourheads and Nagus Hendrickson, our senior producers. Carl Kevin Robinson Jr. Is our associate producer. Our theme music was composed and performed by Hanness Brown. Philip Corne did voiceover,

and Bob Langrath and Sultan Shimon contributed reporting. Rick Shine is our editor. Francesca Levi is the head of Bloomberg Podcasts. Be sure to subscribe if you haven't already, and if you like this episode, please leave us a review. It helps others find out about the show. Thanks for listening.