20 BARRON’S September 2, 2019
the European Union by 2030.
The second drug in the company’s pipeline,
which will treat a liver disease called ornithine
transcarbamylase deficiency, would be the first
available drug to treat the underlying causes of
the disease. Yang forecasts 2030 sales in the EU
and the U.S. at $600 million, though safety trials
for the drug have yet to begin.
So will the science work?
Daniel Anderson, a professor of chemical engi-
neering at the Massachusetts Institute of
Technology who has been doing research for
Heartlein’s group for years, said that a major
validation of the technology came in August of
last year, when the FDA approved a drug
called Onpattro, made by Alnylam Pharma-
ceuticals (ALNY).
Onpattro, which treats a rare genetic disease
called hATTR amyloidosis, works by entering
liver cells and knocking out mRNA molecules.
To get into the cell, the drug uses a lipid nano-
particle—the same delivery device used by the
mRNA therapies.
“For everybody working on messenger RNA,
we can point to that and say look, you can do
it,” Anderson said. “It’s not exactly the same,
but it’s not some science-fiction story.”
Anderson, who looks a bit like Robert F.
Kennedy, is a lipid nanoparticle guru. He de-
signed the lipid nanoparticle that Translate is
using in its second treatment, which targets a
rare liver disease, in his lab at MIT’s Cam-
bridge campus. There, postdocs and graduate
students work at long tables amid bottles, pi-
pettes, high-tech liquid handlers, and old-fash-
ioned Schlenk lines.
At the lab, grad student Allen Jiang han-
dled a chunk of plastic with tiny channels
drilled through it. To make an experimental
mRNA drug, Jiang shot synthetic mRNA into
one hole and lipids into another. They combine
in the channel, the lipids wrapping themselves
around the mRNA to make a lipid nanoparti-
cle. Jiang and his colleagues experiment with
novel lipids to test new ways to deliver the
synthetic mRNA, and then dose mice to see if
it’s working.
“What you really want is to get the most effect
for the minimal amount of nanoparticle,” Ander-
son said. “We think if we can get the vehicle to
work great, it can be used for many diseases.”
The tests in mice are ongoing. Of course,
mice are a long way from people.
“There are a lot of really exciting data in a
range of different model systems that make us
think it is really going to work,” Anderson said.
“The human data we get over the next few
years will help us determine how broadly
mRNA technology can be used.”
Other experts say that the challenges of mak-
ing it work in people shouldn’t be underestimated:
“It sounds very promising. Why don’t we see
more?” asks Xiling Shen, a professor of biomed-
ical engineering at Duke University, who has
studied mRNA therapies but doesn’t focus on
the field.
The fact that an mRNA therapy would need
to be taken regularly, like a normal drug, could
make it safer than gene therapies. But it also
means that the risk of an unwanted and danger-
ous immune reaction is greater.
“If you repeatedly inject something foreign,
you can cause an immune response in the body,”
Shen said. He added that the transient nature
of the therapy makes delivery of the drug very
challenging. Can you get enough mRNA into
the body to produce enough proteins for a
human patient to experience an effect?
The answers are coming soon.
At Translate Bio’s lab in
Lexington, Mass., teams of
scientists and technicians
are working on curing
diseases with mRNA.
Tell Us What
You T hink
Would you take a
gamble on investing in
mRNA? And what do
you think the future of
biotech will be?
Write us at mail@
barrons.com and we
may publish your take.
Find out more at
barrons.com/mailbag.
Placing Bets
On Biotech
Disruption
For investors, there are a handful of ways to
get comfortable with a gamble on mRNA.
The strongest endorsement of Moderna
(ticker: MRNA) and Translate Bio (TBIO) may
have come from Big Pharma. AstraZeneca
(AZN) is among the largest shareholders of
Moderna, with a 7.7% stake, and has three
separate drug-development deals with the
company. Merck (MRK) has another two.
Translate has a drug-development deal with
Sanofi Pasteur. Takeda Pharmaceutical
(TAK) owns 13.9% of Translate; GlaxoSmith-
Kline (GSK) has another 6.3%.
One way to make hedged bets on mRNA is
through companies such as AstraZeneca and
Merck, which are set to profit if Moderna’s
technology begins to work out.
Two private German companies are also
major players. CureVac, based in Tübingen,
was focused on mRNA-powered prophylactic
vaccines until its new CEO, Dan Menichella,
took over last year and reoriented the com-
pany’s efforts toward oncology and rare dis-
eases. Mainz-based BioNTech, which develops
mRNA-powered personalized cancer vaccines,
raised $325 million in July, with an enormous
valuation that makes it the European version
of Moderna. Neither is expected to go public in
the near term, but both could be promising
opportunities if they do.
Another public company, Arcturus Ther-
apeutics Holdings (ARCT), is also pursuing
mRNA therapies. It is smaller than Translate,
with operating expenses of $10.7 million for
the most recent fiscal quarter, compared with
Translate’s $29.4 million.
Moderna’s broad approach to drug devel-
opment could give investors confidence; the
company doesn’t need to bat a thousand to
succeed. And the vaccine business may be
argument enough.
“There are only a couple of technologies
that can serve vaccine markets,” says Chris-
tian Koch, a member of the investment man-
agement team at BB Biotech, a Swiss biotech
investment company that holds Moderna. “One
is the classical approach....That has been en-
trenched in Big Pharma, due to the scale and
breadth of manufacturing and distribution.”
With the advantages offered by mRNA,
Moderna could handle the manufacturing, Koch
says. Distribution remains an issue, but he
says that the vaccines remain an investment
argument for his firm.
For other investors, the wisest bet may to
let the Big Pharma business-development de-
partments do the research for you, and be
ready to wait a good long while for profitabil-
ity. That points to Moderna, and perhaps to
Translate Bio—and to a lot of patience.
—JOSHNATHAN-KAZIS