December 7, 2021 • 27 mins
Covid-19 is just the beginning for messenger RNA vaccines. Researchers are testing shots across a range of diseases, from cancer to malaria, HIV or even multiple sclerosis. There’s no guarantee the technology will work beyond infectious diseases, but if it does, it could transform medicine.
See omnystudio.com/listener for privacy information.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
A black van with tinted windows is parked in front
of an Art nouveau building not far from Munich's English garden.
It's September. The COVID nineteen vaccine drive is in full swing,
with countries around the world debating just who should get
booster shots. Inside the Munich villa's heavy door is a
(00:21):
narrow entry foyer that leads up a wooden staircase. There's
a cluster of people coming down. It's Germany's star scientists
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
(00:41):
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
(01:02):
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
(01:28):
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
(01:49):
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
(02:11):
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
(02:37):
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
(03:00):
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.
(03:22):
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
(03:43):
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
(04:03):
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
(04:24):
from the Prognosis podcast. This is Breakthrough. That's the sound
(04:47):
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
(05:08):
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
(05:30):
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
(05:51):
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
(06:15):
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
(06:40):
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
(07:01):
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
(07:23):
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
(07:46):
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
(08:07):
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
(08:29):
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
(08:52):
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
(09:14):
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
(09:36):
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,
(10:00):
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,
(10:22):
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
(10:44):
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
(11:04):
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
(11:27):
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.
(11:49):
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
(12:10):
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
(12:34):
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
(12:58):
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.
(13:21):
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
(13:41):
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
(14:06):
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
(14:27):
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
(14:51):
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
(15:15):
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,
(15:36):
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.
(16:01):
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
(16:23):
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
(16:47):
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,
(17:09):
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,
(17:29):
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
(17:51):
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
(18:11):
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
(18:34):
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
(19:00):
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.
(19:21):
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
(19:44):
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
(20:05):
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
(20:26):
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
(20:47):
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
(21:07):
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.
(21:32):
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
(21:54):
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
(22:15):
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
(22:38):
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,
(23:03):
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
(23:25):
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.
(23:48):
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
(24:09):
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
(24:32):
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
(24:54):
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
(25:14):
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
(25:35):
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
(25:55):
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,
(26:43):
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
(27:06):
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,
(27:28):
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.
A black van with tinted windows is parked in front
of an Art nouveau building not far from Munich's English garden.
It's September. The COVID nineteen vaccine drive is in full swing,
with countries around the world debating just who should get
booster shots. Inside the Munich villa's heavy door is a
(00:21):
narrow entry foyer that leads up a wooden staircase. There's
a cluster of people coming down. It's Germany's star scientists
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
(00:41):
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
(01:02):
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
(01:28):
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
(01:49):
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
(02:11):
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
(02:37):
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
(03:00):
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.
(03:22):
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
(03:43):
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
(04:03):
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
(04:24):
from the Prognosis podcast. This is Breakthrough. That's the sound
(04:47):
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
(05:08):
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
(05:30):
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
(05:51):
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
(06:15):
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
(06:40):
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
(07:01):
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
(07:23):
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
(07:46):
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
(08:07):
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
(08:29):
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
(08:52):
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
(09:14):
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
(09:36):
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,
(10:00):
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,
(10:22):
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
(10:44):
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
(11:04):
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
(11:27):
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.
(11:49):
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
(12:10):
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
(12:34):
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
(12:58):
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.
(13:21):
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
(13:41):
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
(14:06):
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
(14:27):
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
(14:51):
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
(15:15):
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,
(15:36):
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.
(16:01):
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
(16:23):
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
(16:47):
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,
(17:09):
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,
(17:29):
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
(17:51):
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
(18:11):
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
(18:34):
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
(19:00):
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.
(19:21):
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
(19:44):
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
(20:05):
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
(20:26):
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
(20:47):
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
(21:07):
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.
(21:32):
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
(21:54):
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
(22:15):
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
(22:38):
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,
(23:03):
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
(23:25):
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.
(23:48):
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
(24:09):
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
(24:32):
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
(24:54):
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
(25:14):
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
(25:35):
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
(25:55):
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,
(26:43):
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
(27:06):
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,
(27:28):
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.
Popular Podcasts
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations.
The Nikki Glaser Podcast
Every week comedian and infamous roaster Nikki Glaser provides a fun, fast-paced, and brutally honest look into current pop-culture and her own personal life.
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.