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