22 BARRON’S September 28, 2020
[ARCT] are also involved. BioNTech,
which has partnered with Pfizer
[PFE], recently announced they had
taken their fifth Covid vaccine
construct into the clinic. That is either
very confidence-inspiring, or very
concerning.
Whatsaytherestofyou?
Celniker: I agree with Geoff from a
safety perspective. I can’t guess on the
efficacy perspective at this point. When
there are problems with vaccines, it is
often related to the adjuvant
component. Going with tried-and-true
adjuvants can really make a difference.
From a safety standpoint, traditional
vaccines with known adjuvants are
going to get the most uptake.
Yoon: We don’t know how long
immunity is going to last, so the ability
to re-dose is going to be an important
factor. You may lose immunity with the
viral-vector approach.
Is there skepticism about some of
the newer technologies, such as
Moderna’s messenger RNA
approach?
Porges: We are cautious about the
tolerability and duration of the immune
response to mRNA. Yet, we have seen
that these products are generating
antibodies and T-cell responses.
Progress is being made. I mentioned
that many trial subjects are getting high
fevers. The first job of a vaccine
developer is to do no harm, because
your subjects aren’t patients. They are
healthy consumers, and their risk of
having a catastrophic event tied to the
disease is very low. Venturing headlong
into a novel technology with a
dramatically accelerated timeline to
market and an abbreviated regulatory
process is alarming to many people in
the vaccine industry. Presumably, some
people have other views.
Celniker: Another issue to consider is
which vaccines can be produced fastest
and distributed to the broadest number
of people. Maybe you start with a
vaccine that is easier to make, more
stable, and better to distribute, and
then follow on with more validated
vaccines with more robust safety
profiles and durability.
Which of the companies developing
Covid treatments deserve investors’
attention?
Porges: Merck [MRK] has partnered
with Ridgeback Biotherapeutics on an
oral antiviral going into a pivotal set of
trials. It is likely to be suitable for
outpatient use. I don’t know that it will
have the potency of Gilead’s remdesivir.
If I were in the hospital with the
coronavirus, I’d definitely want
remdesivir, but the bullish news about
remdesivir has been washed out of
Gilead’s stock by now.
Several companies participate in the
convalescent-plasma market, but
convalescent-plasma treatments have
been a bit of a disappointment. Now we
are pivoting toward the use of
monoclonal antibodies; Eli Lilly [LLY]
and Regeneron Pharmaceuticals
[RGEN] are in the forefront there. I
expect those products to be approved
on an emergency basis by the end of
the year, with full approval in the first
part of next year. AstraZeneca [AZN]
is testing an antibody therapy, Vir
Biotechnology [VIR] has partnered
with GlaxoSmithKline, and Amgen
[AMGN] is developing one. I’m most
positive about Regeneron’s approach
because it combines two antibodies.
Some viral substrates seem to be able to
avoid the pressure of a single antibody,
but it is difficult to create a substrate of
the virus that avoids two antibodies
simultaneously.
How likely is a second wave of
Covid cases, once people head back
indoors?
Celniker: People need to understand
the importance of continuing to
distance and wear masks. Also, we
need to get more businesses
comfortable with working remotely.
We’ve seen what happens when
businesses open up and people go
indoors too soon.
Porges: I have two questions for my
colleagues: How do you do due
diligence on new investments when
you’re working remotely, and how do
you onboard new employees?
Casdin: First, I agree that we will see
flare-ups this winter, recognizing that
we are going to be inside more often.
Second, our investment due-diligence
process hasn’t really changed, except
that we can’t go to medical meetings
and experience those serendipitous
post-session conversations. But we still
conduct calls with KOLs [key opinion
leaders] on a daily basis, and connect
with dozens of public and private
companies. Our process is structured
to enable defined information-exchange
points throughout the day, which is the
key to working and investing in a
decentralized environment.
We are invested in many private
companies, including some of Abbie’s
and Third Rock’s companies. The data
we need to make decisions is still
available in structured data rooms.
Management teams and scientific
leadership remain accessible. Everyone,
including companies, is doing a good
job of communicating. We can’t tour
the labs, but we’ve seen many labs, and
they all look pretty much the same. We
have built trusted partnerships and pay
particular attention to the investor
syndicates behind the companies in
which we invest.
Celniker: Onboarding new employees
is tough. Many are young and come
from social settings, such as schools
and labs, where they have done
graduate work. They are looking for a
similar experience in the office or the
lab. Our labs are mostly at 100%
capacity because they have never been
so filled with people that they couldn’t
work with the appropriate social
distancing.
Casdin: That’s an important point. Life
sciences is uniquely positioned in the
Covid environment because lab work is
shift work. It is easier to stay six feet
apart. The business of research and
development never really stopped, the
way hotel and restaurant work and the
travel industry did.
Looking beyond Covid, what are the
most exciting developments in
health care and life sciences today?
Celniker: There is a ton going on.
Many new companies have been
launched during this period. On March
15, we were afraid the sky was falling.
By April 15, we couldn’t keep up with
the science. Eddie talked about the
supply-chain aspect of Covid. Some
unbelievable tools are being developed
to support modern drug discovery. You
will be able to invest in companies
applying new tools to discover drugs to
solve problems that couldn’t be solved
five years ago. The technology will now
allow us to hit targets that couldn’t be
hit before. A diversity of therapeutic
areas—whether cancer, or autoimmune
diseases, or hearing loss—can be
supported by these tools, which are
powered by computational biology,
artificial intelligence, and machine
learning.
We recently launched a company
called MOMA Therapeutics that plans
to develop small-molecule drugs
against a family of proteins using ATP
[adenosine triphosphate] hydrolysis to
generate energy to drive cell processes.
The industry never could have
imagined going after the ATPase
target-class without some of these new
technologies. In another area, we are
working on transcription factors
[proteins that help to turn specific
genes on or off by binding to DNA].
Transcription factors are the keys to all
biology. Today, there are drugs that
modulate transcription factors, but
they were discovered serendipitously,
not through a focused and intentional
approach.
Does that mean the pandemic hasn’t
slowed progress in non-Covid
areas?
Casdin: It has accelerated progress
and capital inflows, and removed
certain barriers. We recently spoke
with Jay Bradner, president of the
Novartis Institutes for BioMedical
Research, and he commented that
seeing how quickly his team spun up
trials around Covid caused him to say
he would never go back to the timelines
that were accepted pre-Covid. The
speed with which the industry has
responded to this crisis has changed
the way people perceive what is
possible for clinical-trial timelines. I
suspect this is a permanent change.
The pandemic has kick-started, or
accelerated the entire life-sciences
industry.
Porges: Nothing accelerates
technology development like a big war.
Eli is right: The industry has seen huge
capital inflows. So many life-sciences
companies are raising money. We are
seeing dramatic advances in
technology, not just in the vaccine area
but in the diagnostics field. Cancer
“The speed with which the industry has
responded to this crisis has changed the
way people perceive what is possible for
clinical-trial timelines.” Eli Casdin