Translating a Recent Scientific Discovery about Covid19
well hello everybody who’s
listening uh virtually um my name is
bruce patterson
and i’m a virologist uh you probably
haven’t heard of virologists
in the past but all of a sudden now
i think we’re in the middle of an era
where we we need
uh virologists you’re going to see me
smile
and be relatively hopeful because i am
hopeful
the other thing is we’ve already saved
lives with the approach
that i’m going to talk about and we’re
hoping to save even more lives
as we go through fda clinical trials
with an exciting new drug
that we developed based on
a discovery that i’ll talk about
shortly now everybody’s heard about
kovid
there’s so much information out in the
media
and in the world about how it works and
how infectious it is and
i hope to at least address some of those
issues
i came back from china in january
talking to a company over there about
doing a deal when i first heard about
this virus
that that was emerging
and it brings up a very interesting word
that we’re hearing a lot about which is
emerging infections and what does
emerging infections mean
it means they’re infections that our
bodies haven’t
seen before so that’s a very interesting
conundrum for the human body because
we basically have a storage vault
of immune responses against pathogens
bugs bacteria viruses
uh parasites that the body uses
when you’re infected with those uh with
those
particular pathogens again emerging
infections are something that our body
has never seen before
but the body actually has some very
elegant ways
uh rudimentary ways although
that to fight off these emerging
infections
and that’s part of what i’m going to
talk about because that’s part of what
happens
uh in covid okay so where do we do all
this work well
my company in cell dx specializes
in developing novel approaches to both
diagnosing
uh particular pathogens looking at how
the pathogens work
uh working with companies that have
therapeutics
that can potentially work for these
pathogens
and then most importantly using the
diagnostics to say that the
therapeutic is actually working so
we’ve all heard about the different
diagnostics and the shortage of
diagnostics
that are out there uh in the world and
those really revolve around
do you have the virus yes or no that was
the first wave of diagnostics
the second wave of diagnostics was have
you been exposed to the virus
and do you have immunity to the virus
now those are two
very different questions but the third
level of diagnostics that we started
thinking about over two months ago
was how can we design diagnostics and
laboratory tests that say whatever we
try on a patient is actually working
and that’s the whole area of
personalized medicine that we’re in
these days
and usually we apply that to cancer but
the fact is personalized medicine can
also be applied
uh to infectious disease and that keeps
patients from having to take every
one drug or another drug and act as a
guinea pig until one of them works
we want to know before you get a drug
when it’s going to work
how it’s going to work when do you give
it and how much do you give
and most importantly is the drug safe
so we hear a lot about the drugs are out
in the market about covid
and the fact is the big question are
they really safe
do they cause kidney problems they cause
liver problems
are they immunosuppressive like the big
dexamethasone that we’ve heard over the
last few days which is
basically a steroid that completely
immunosuppresses
individuals who are already
immunosuppressed
well i’ll digress back to covet and the
whole covid
story right now when we first
looked at covid it was very interesting
because we saw
patients who look very much like aids
patients
aids patients have low quote cd4
lymphocytes which is part of the immune
system against viruses
the other cell that’s involved in the
immune system against viruses is called
a
cd8 t cell whereas aids has
low cd4 counts covate has very low cd8
counts
but the the but at the end of the day
they create the same situation
that is immunosuppression so what do we
see in covid patients
well it’s very interesting i’ll skip
forward a couple of slides
we now know that covid goes in about two
different phases there’s an initial
phase which we call the virologic phase
you’re infected you have a positive
covid test
maybe you feel okay but the virus is in
your body
and it’s replicating maybe it progresses
maybe it doesn’t that’s one of the
biggest questions
and i would say that one of the biggest
concerns about kovid
is that it’s unpredictable you know this
is my
fourth pandemic i
started my career in hiv
which developed a lot of the tools that
we’re using today
in covid and then i was a head of
virology at stanford during
sars one and the h1n1
flew in the late late 2000s
and there are very similar themes
in all of these pandemics however
kovid is one that has been highly highly
unpredictable
it starts out as a viral disease but at
some tipping point which you see in the
middle of this slide
it goes from being a virologic disease
to an
immunologic disease and it’s the
immunologic disease
in its severest form that causes the
damage of the lungs
the damage to the kidneys the damage to
the liver the coagulation that you see
with strokes
amputations that were seen recently and
even
in kids a disease that’s similar to
what’s called
kawasaki’s disease which is basically
extreme
inflammation of blood vessels including
the coronary arteries
that can cause death in some of these
kids
as i’m saying this you can see how
unpredictable and unusual this viral
infection is in terms of all the
different manifestations that it causes
well what is this switch in the middle
of this slide
that causes covid to go from a virologic
disease
to an immunologic disease now that was a
big question two and a half months ago
when i was working with my chinese
colleagues
and trying to figure out what was
happening we were in the middle of
developing some tests for them
we looked at what was called cytokines
cytokines are proteins that are made by
immune cells
and other cells to basically confer
function on your body’s immune system
for the most part and cytokines are
involved in
moving cells around your body to fight
off these different pathogens no matter
where they are
so it’s a very interesting set of
proteins that get released
into the circulation and we found very
high levels of this one protein called
rantes
or ccl5 in all of these patients across
the board
in covet infection why is that important
well rantes is like a magnet
when rantis is produced it pulls immune
system
immune cells from all over your body
into these areas of inflammation
right now that’s fine that’s what it’s
supposed to do
except when it’s overactive and
unlike some of the other proteins that
make up what’s called the cytokine storm
which is
what everybody’s hearing about on cnn
and other shows which is just this
mass release of these proteins that are
supposed to confer
immune functions but it’s it’s
overzealous
it’s hyper immunity and it’s actually
causing lung damage and kidney damage
and liver damage
and coagulation that’s a problem
but it’s all being driven by the fact
that this one protein rantes
is pulling in the cells that make these
proteins that make up the cytokine storm
so what does that mean for us in terms
of therapies
and for vaccines for that matter well
the fact is
with emerging infections we don’t have
any tools any drugs any vaccines
that are specific for the emerging
pathogen and that’s a big shortcoming in
terms of the world and how we prepare
for the next pandemic we need to have a
stockpile of drugs
that have a general broad
application against pathogens that we
may not even know about
because it’s going to take 12 to 18
months to come up with pathogen-specific
therapies or vaccines for that matter
and so you know what can we do about
that well
what we’ve learned in cancer over the
past five years
is the most powerful drug against
cancer is our own immune system
we found drugs like optivo and katruda
and some of these others
that bring back the immune response
against tumors okay there was a case
when i was working with a large
pharmaceutical company
where there was a melanoma the size of a
golf ball
they took 12 months of one of these
quote immuno oncology drugs
that restored the immune response and by
the end of 12 months it was the size of
a freckle
and you could scrape it off with a
scalpel blade
now my original thinking back two and a
half months ago when we had this
emerging infection is
let’s manipulate the immune response
like we’re manipulating the immune
response in cancer
let’s do that to this virus
and see what happens and in fact
when we found this rantes there was a
great drug called larondemab
that actually blocks the binding of this
rantes to immune cells
and actually prevents this mass
migration of cells
into non-specifically into the lung and
other organs
and relieves uh and quiets
this storm of bad proteins that are
causing all the the immune damage in
these patients
and in addition it restored the
immunosuppression so these patients were
horribly immunosuppressed
they took the drug and their their
levels of their lymphocytes their cd8
cells went back to normal
then surprisingly unlike this drug wren
desevere which was just approved which
is the antiviral
this drug laron lamab actually dropped
the amount of virus it shut off the
viral replication
and by 14 days the viral burden
was zero okay
now the biggest question when this rem
deserver got approved was
why is this antiviral not shoving off
virus
and that’s what led me to be skeptical
about that as a therapy
because the three things you need in
covid are
a quiet this so-called cytokine storm to
prevent all the lung damage and
organ damage b restore the immune
response because these patients are
immunosuppressed and could die of
bacterial infections
or other viral infections and c
stop the virus now
the government fauci and others have
proposed well that may take
two drugs well what’s fascinating about
our study that we
we we just published uh in the pre-print
journal
uh was that this drug laurentlamab did
all three of those it quieted the
cytokine storm
it restored immunosuppression and it
dropped the virus
what more than you need in in covid
so the goal for covid therapy
is really to address these phases of
disease
and like i said it’s very very
unpredictable
we don’t know which patients are going
from this virologic phase
to the immunologic phase there’s not a
marker although we think
rantis may be that marker the the
protein that we discovered
at ncdx and the fact is this drug
laurentlamab
in early phases may prevent the
transition from
virologic or mild disease to severe
disease
and in late disease would reverse all of
these changes
in immunosuppression that i just
mentioned
and the fact that i’m smiling or at
least
glowing a little bit is the fact that
this drug has saved lives
at the end of the day we have already
saved lives
would we love to save more absolutely
we’re in the middle of two
big uh fda clinical trials one for mild
to moderate disease
one for severe disease and if it turns
out how we
expect and again we’ve seen data on
hundreds of patients
over multiple multiple weeks of therapy
we’re hopeful and we’re excited about
the possibility
that this drug can keep patients from
going from mild disease to severe
disease
and in the severest of diseases
save lives and and that is
the goal of all covid therapy and that
is a therapeutic
now everyone’s talking about the
vaccines and how quickly they’re they’re
coming out
big lesson from hiv okay we used to hear
reports about
successful trials of vaccines
yeah phase one they were safe you could
give the vaccine and they wouldn’t get
hiv
right so the two biggest hurdles in
vaccines
are does it make antibodies
that help fight off infection
and are those antibodies effective those
are the two big hurdles that remain
for for vaccines this virus mutates
uh and has high sequence variability
around the world
so you know it’s it’s not quite as
mutating as uh as hiv but you know
that gives me pause as well about the
ultimate efficacy of vaccines
but i’m very hopeful that we have
therapeutics
and if we have therapeutics that prevent
death
and therapeutics that prevent morbidity
i we can get back to work this becomes
just another
viral infection like the influenza
or or other respiratory viruses that we
get in the winter
because it’s something that we can deal
with and we can prevent the death
the problem was in covid which is also
worrisome with
with the relaxation of all these um
shelter in place and of course we’ve
seen a massive
increase in cases due to that
my concern is people talk about
infection rates
and they talk about death rates and they
say the death rate is
relatively low relative to ebola and
maybe some other viruses
however nobody talks about the morbidity
in this disease this is not about do i
live or do i die
in the people who died relatively small
percentage
the problem is these people who get
infected
and have severe infection are not
better if you look at this graph
it goes out to 30 days 30
days after infection some people
have not gotten back to normal when we
get the flu
we get other respiratory viruses in the
winter we stay in bed for a week
we we we get our strength back a little
we go back to work the next week we’re
still a little weak maybe a little tired
but
at the end of two weeks you’re back in
the gym and you’re feeling fine
that is not the case in covid and we’re
not talking about it
these people are 30 days out 40 days out
their their their cytokines all their
blood work that i’ve been working with
in
hundreds and hundreds of patients over
time
30 days 40 days it’s not
normal it’s not back to normal and all
this inflammation
is making them not feel well
and there is the possibility that this
inflammation is doing damage
rantes this protein that we discovered
that i’m talking about
uh has been implicated in renal failure
has been implicated in liver you know
liver toxicity
has been implicated in coagulopathies or
coagulation
which is strokes and clots and all the
things you’re hearing about
these people who have to have
amputations
it’s all being driven by massive massive
amounts of inflammation and the hope is
drugs like laura momab will be able to
to be able to treat that but we have to
treat that for a long period of time
potentially
and rantes is a marker to tell us when
do you start treating because when do
you do
make that switch from a viral disease to
an immunologic disease
and how long do you treat but that’s
what our ability is in medicine right
now
is to give a drug and know what it’s
doing
we no longer use patients as guinea pigs
and let’s give this a try
let’s give that a try we know when to
start a therapy we know when to stop a
therapy
and ultimately that not only saves the
patient
pain and suffering but also saves health
care dollars
and i think some of the other talks
today are going to be the health care
and the economic implications of covid
which we also have to take into account
as we’re
moving forward uh with some of these uh
approaches but again i’m very hopeful
and i’m hopeful that we have a drug that
we have a therapy
that will remove the specter of death
remove the specter of horrible
morbidities
and makes this just another infection
and we can go about our business get
back to work
and get this economy restored
thank you i really appreciate the tedx
folks for inviting me it’s been very
exciting to do this
in my home uh country up here in
northern michigan and uh
be safe be well we’re working on it
thank you very much