Good morning.
My
name
is
Rob,
and
I
will
be
your
conference
operator
today.
At
this
time,
I
would like
to
welcome
everyone
to
the
argenx
Fourth
Quarter
and
Full
Year
2021
Conference
Call.
All
lines
have
been
placed
on
mute
to
prevent
any
background
noise.
After
the
speakers'
remarks,
there
will
be
a
question-and-answer
session.
[Operator Instructions]
Thank
you.
Beth
DelGiacco,
Vice
President,
Investor
Relations
and
Corporate
Communications,
you
may
begin
your
conference.
B
Beth DelGiacco
Thank you,
operator.
A
press
release
was
issued
earlier
today
with
our
full
year
2021
financial
results
and
the
recent
business
update.
This
can
be
found
on
our
website
along
with
the
presentation
for
today's
webcast.
Before
we
begin,
I'd
like
to
remind
you
on
slide
2
that
forward-looking
statements
may
be
presented
during
this
call.
These
may
include
statements
about
our
future
expectations,
clinical
developments,
regulatory
timelines,
the
potential
success
of
our
product
candidates,
financial
projections
and
upcoming
milestones.
Actual
results
may
differ
materially
from
those
indicated
by
these
statements.
argenx
is
not
under
any
obligation
to
update
statements
regarding
the
future
or
to
conform
these
statements
in
relation
to
actual
results,
unless
required
by
a
law.
I'm
joined
on
the
call
today
by
Tim
Van
Hauwermeiren,
Chief
Executive
Officer;
Karl
Gubitz,
Chief
Financial
Officer;
and
Keith
Woods,
Chief
Operating
Officer.
I'll now turn the call over to Tim.
T
Tim Van Hauwermeiren
Good
morning
and
thank
you
for
joining
our
call
today.
We
had
a
truly
monumental
2021
and
ended
the
year
with
the
FDA
approval
of
VYVGART,
a
first
of
its
kind
FcRn
blocker
for
the
treatment
of
generalized
myasthenia
gravis
in
adult
patients
who
are
acetylcholine
receptor
antibody
positive.
It
was
a
milestone
we
have
been
working
towards
for
many
years,
and
we
were
so
gratified
to
be
able
to
honor
our
commitment
to
patients
by
bringing
them
a
new
treatment
option.
The
regulatory
momentum
continued
into
2022 with
the
subsequent
approval
of
VYVGART
in
Japan
just
34
days
later.
I
cannot
emphasize
enough
the
work
it
took
for
our
teams
to
make
this
happen
seamlessly.
I
want
to
start
our
call
today
talking
about
our
launch.
During
these
first
weeks,
we
have
focused
primarily
on
demand
generation
through
education
and
awareness
efforts.
Keith
will
share
some
metrics
later
in
the
call,
but
we
still
have
a
lot
to
learn
about
our
launch
trajectory
in
the
coming
quarters.
We
are
doing
our
best
to
characterize
the
state
of
the
launch
today,
though
it's
fair
to
say
it's
still
very
early.
And
these
are
not
necessarily
metrics
we
will
share
on
an
ongoing
basis,
especially
as
we
start
to
provide
revenues
during
our
Q1
earnings
call
in
May.
I
have had
the
privilege
of
being
on
the
road
with
many
members
of
our
field
team
since
the
start
of
the
launch.
At
a
high
level,
we
are
encouraged
by
the
initial
demand
in
our
launch.
We
know
that
it
is
still
early
days
and
that
we
face
the
same
challenges
that
we
described
at
approval.
COVID
restrictions,
the
lack
of
a
J
code,
the
need
for
physician
education
and
better
awareness,
but
eight
weeks
into
the
launch,
we
are
cautiously
optimistic
and
trending
well
against
our
plans.
I
have
also
been
encouraged
by
the
feedback
I'm
hearing
firsthand
from
our
physicians
all
of
which
is
consistent
with
many
of
the
messages
we
shared
leading
up
to
approval.
On
slide
4,
for
example,
the
unmet
needs
faced
by
gMG
patients
for
new
therapies
is
significant,
and
we've
seen
real
demand.
The
challenge
for
our
salesforce
has
been
demonstrating
a
sense
of
urgency
during
a
time
when
patients
do
not
see
their
doctors
regularly.
We
also
see
physicians
rethinking
how
to
treat
their
patients
based
on
the
efficacy
and
safety
profile
we
demonstrated
[ph]
in
adults. (00:04:42)
And
finally,
doctors
applaud
individualized
dosing
and the VYVGART
label,
which
allows
them
the
flexibility
to
dose
based
on
clinical
evaluation.
In
MG,
where
every
patient
is
unique
and
experienced
the
disease
course
differently,
an
individualized
approach
makes
sense
to
physicians.
We
believe
that
the
treatment
cycle
approach
will
accommodate
the
majority
of
our
patients.
We
also
want
to
consider
the
individual
needs
of
patients
that
may
require
alternative
or
more
continuous
dosing
and
to
have
data
should
we
get
questions
from
providers
on
this
topic.
We
started
a
Phase
3b
trial
called
ADAPT
NXT
to
evaluate
additional
dosing
schedules
that
physicians
could use
to
further
individualize
the
VYVGART
treatment
approach.
As
this
is
a
typical
Phase
3b
trial,
we
will
not be
providing
additional
updates
on
the
study
outside
of
an
upcoming
medical
meeting.
In
general,
we
want
to
have
the
most
complete
offering
for
patients
and
physicians,
whether
on
a
dosing
schedule
or
around
formulation,
IV
or
subcu.
We
continue
to
believe
that
having
both
an
IV
and
subcu
option
will
be
important
to
capture
variability
in
patients
and
physicians
preferences.
Slide
5.
Our
Phase
3
ADAPT
subcu
non-inferiority
trial
is
on
track
to
readout
this
month,
evaluating
subcu
efgartigimod
which
is
co-formulated
with
Halozyme's
validated
ENHANZE
technology.
In
this
trial,
we
aim
to
bridge
IV
to
subcu,
based
on
PD
effect,
specifically
IgG
reduction
at
day
29.
We
designed
our
innovative
bridging
trial,
based
on
a
few
key
points.
First,
we
observed
in
our
clinical
trials
a
linear
correlation
between
IgG
reduction
and
clinical
benefit
in
gMG.
We
also
see
a
consistent
PD
effect
with
efgartigimod
whether
in
healthy
volunteers
or
gMG
patients.
The
disease
biology
of
gMG
does
not
affect
PD,
and
actually,
we
have
seen
this
in
all
indications
we
have
studied
so
far.
And
finally,
in
our
Phase
1
study
of
subcu
efgartigimod,
we
observed
an
identical
PD
effect
with
a
fixed
dose
of
1,000
mg
subcu,
as
with
10
milligram
per
kilogram
IV.
Beyond
the
non-inferiority
primary
endpoint,
ADAPT
subcu
will
capture
additional
safety,
efficacy
and
PK-PD
data
in
the
secondary
endpoint
analysis,
which
will
be
important
for
our
commercial
team.
ADAPT
subcu
also
serves
to
satisfy
our
safety
database
requirements
For
subcu
efgartigimod.
We
enrolled
more
than
the
50
patients
required
for
the
primary
endpoint
analysis
and
allowed
ADAPT
open
label
extension
patients
to
roll
over
to
the
ADAPT
subcu
trial.
We
expect
to
be
able
to
give
you
an
update
on
timing
of
our
BLA
filing
when
we
report
top
line
results.
ADAPT
subcu
is
the
first
of
our
near
term
data
milestones.
We
also
are
on
track
to
share
results
in
the
second
quarter
from
the
advanced
trial,
evaluating
IV
efgartigimod
in
primary
immune
thrombocytopenia.
Slide
6.
We
designed
our
Phase
3
ADVANCE
trial
based
on
the
results
from
our
Phase
2
and
benchmarking
of
peer
ITP
trials.
In
our
Phase
2,
we
had
ambitiously
dosed
patients
for
just
four
weeks
while
monitoring
platelet
counts
out
to
21
weeks.
We
learned
from
this
trial
that
more
chronic
dosing
is
required
in
this
population,
even
with
the
limited
drug
exposure,
we
saw
responses
across
patient
types
in
a
very
refractory
ITP
population.
These
results
are
published
in
the
American
Journal
of
Hematology.
We
also
saw
a
high
placebo
response
in
our
Phase
2,
which
in
looking
at
these
trials
is
very
common
in
ITP
given
the
fluctuating
nature
of
platelets.
In
our
Phase
3,
we
are
dosing
patients
weekly
for
26
weeks
with
the
potential
to
push
the
cadence
to
biweekly
dosing
based
on
a
stable
platelet
count.
We
are
measuring
the
primary
end
point
between
weeks
19
and
24,
where
a
patient
has
to
have
a
stable
platelet
count,
meaning
over
50,000
platelets
per
microliter
in
at
least
four
of
those
six
visits.
By
managing
placebo
response
with
this
stringent
endpoint,
we
are
also
setting
the
efficacy
bar
high
for
our
treated
patients.
It
will
be
important
to focus
on
the
delta
between
response
in
the
active
and
placebo
groups.
The
secondary
endpoints
will
also
be
important
with the
advanced
readout
including
safety
and
tolerability,
cumulative
platelet
counts,
bleeding
events
and
quality
of
life
data.
This
will
show
a
more
complete
picture
of
where
efgartigimod
could
play
a
role
in
IgG.
We
hear from
physicians
that
there
remains
a
high
unmet
need
in
ITP
and
that
long-term
response
rates
are
not
satisfactory.
Patients
typically
cycle
through
treatment
options
including
through
multiple
TPOs
in
order
to
maintain
a
stable
platelet
count.
Our
hope
is
that
we
can
break
this
cycle
and
if
an
ITP
patient
fails
or
relapses
on
an
initial
TPO,
they
will
be
in
a
position
to
try
efgartigimod
before
his
second
or
third
TPO.
You
can
see
that
we have
a
catalyst
rich
first
half
of
the
year,
between
our
launch
progress,
and
these
two
data
readouts.
It's
a
busy
time,
but
also
a
very
exciting
time
to
finally
have
our
teams
in
the
field
engaging
with
physician
customers
and
serving
patients.
I'm
going
to
turn
the
call
to
Keith
who
will
provide
more
details
on
the
VYVGART
launch
in
the
US.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Thanks,
Tim.
Good
morning.
I'm
happy
to
provide
an
update
on
the
state
of
our
commercial
business.
Our
salesforce
has
been
in
the
field
for
eight
weeks
now.
So
we
are
still
in
the
very
early
stages.
But
overall,
we
are
seeing
encouraging
progress
in
engaging
with
our
key
stakeholders.
Slide
7,
please.
On
our
approval
call,
we
talked
about
our
strategic
imperatives
to
empower
patients,
to
provide
best-in-class
patient
support,
to
ensure
rapid
adoption
from
healthcare
professionals,
and
to
enable
appropriate
access.
I'm going
to
share
some
data
from
each
of
these.
First,
on
the patient,
we're
not
going
to
share
patient
numbers
today,
but
we
are
comfortable
sharing
that
we
are
currently
in
front
of
our
own
projections.
We
designed
our
Phase
3
ADAPT
study
to
enroll
a
broad
patient
population.
Some
patients
who
were
on mestinon
alone
and
very
early
in
their
disease,
while
others
were
much
more
severe
relapsed
refractory.
With
the
initial
scripts
coming
in,
we
see
a
breadth
of
patient
profiles
reflective
of
the
ADAPT
population.
In
the
first
weeks
of
launch,
we
have
also
seen
what
we
believe
is
pent-up
demand
for
a
new
therapy
in
patients
refractory
to
all
other
available
treatment
options.
It
is
too
early
to
know
whether
or
not
this
is
a
one-time
bolus
of
patients,
but
we
see
these
patients
contributing
to
our
initial
demand.
Slide
8,
please.
We
launched
our
unbranded
DTC
campaign
in
January
to
create
awareness
about
gMG.
The
impact
of
the
commercial
and
empowering
patients
is
clear.
The
commercial
was
encouraging
patients
to
learn
about
new
treatment
options,
including
VYVGART.
By
speaking
with
their
neurologist
or
downloading
resources
from
the
website
based
on
early
assessments,
approximately
25%
of
website
visits
and
50%
of
phone
call
inquiries
can
be
tracked
back
to
the
DTC campaign.
Slide
9,
please.
Our
patient
support
program
has
also
been
serving
our
patients
and
healthcare
professionals
very
well,
and
approximately
90%
of
our
scripts
have
come
in
through
My
VYVGART
Path.
We're
now
seeing
scripts
translate
into
infusions,
and
My
VYVGART
Path
has
been
crucial
to
this
effort.
Our
second
strategic
imperative
is
with
the
physician
community.
Slide
10,
please.
Our
salesforce
has
done
a
great
job
of
engaging
with
neurologists.
The
goal
was
to
focus
on
our
top
group
of
targets,
which
includes
about
1,000
neurologists.
These
neurologists
are
tiered
based
on
the
number
of
gMG
patients
that
they
treat,
their
likelihood
to
try
a
new
biologic,
and
their
influence
amongst
other
neurologists.
So
far,
our
sales
team
has
reached
about
60%
of
this
top
target
group.
Among
physicians,
we
have also
seen
impressive
breadth
and
depth
of
prescribers.
Groups
are
not
just
coming
in
from
our
physician
champions,
but
from
a
broad
group,
and
equally
from
academic
settings
as
well
as
the
community.
We have
also
seen
depth
amongst
physician
prescribers,
with
many
writing
scripts
for
two
or
more
patients.
About
60%
of
our
prescribers
have
been
from
the
top
1,000 neurologist
targets.
Our
peer-to-peer
marketing
efforts
launched
in
January,
and
so
far,
we
have
held
six
national
broadcasts
and
57
local
speaker
programs.
We
have
74
fully
trained
physician
speakers
in
these
first
crucial
quarters
to
launch
and
raise
awareness
and
increase
the
education
on
VYVGART.
Finally,
our
work
with
payers.
Slide
11,
please.
We
announced
at
approval
that
we
had
reached
agreements
in
principle
with
several
national
and
regional
payers
to
structure
a
value-based
agreement.
As
of
this
week,
VYVGART's
specific
policies
have
been
published
in
plans
covering
approximately
25%
of
US
commercial
lives.
We're
on
track
to
have
broad
coverage
in
place
by
the
end
of
the
second
quarter.
So
far,
almost
all
of the
policies
are
aligned
to
our
label.
Patients
can
gain
access
if
they
have
previously
been
treated
ineffectively
with
one
or
more
standard
of
care
options,
whether
it's
mestinon,
steroids
or
a
broad
immunosuppressant.
We
are
also
seeing
encouraging
prior
authorization
language
approving
for
6
to 12
months
of
treatment
at
a
time
rather
than
based
on
a
specific
cycle.
All-in-all,
we
are
optimistic
after
the
first
eight
weeks
of
launch,
but
it
is
still
too
early
for
us
to
understand
how
this
will
play
out
into
future
quarters.
We
look
forward
to
updating
you
again
during
our
first
quarter
earnings
call.
Before
I
turn
the
call
over
to
Karl,
I'd
like
to
quickly
discuss
our
global
launch
strategies.
Slide
12,
please.
The
upcoming
regulatory
milestones
are
covered
in
our
press
release.
With
Japan,
we
received
approval
in
January,
but
the
official
launch
will
not
start
until
we
have
a
price.
This
is
typically
listed
in
the
months
following
our
approval.
Our
sales
team
has
been
active
with
neurologists
talking
about
VYVGART
and
the
mechanism
of
action.
They
can
line
up
patients
before
we
have
a
price,
but
we
will
not
be
able
to
start
booking
revenues
until
after
the
official
launch.
In
Europe,
we
expect
approval
in
the
second
half
of
the
year.
And
of
course,
regulatory
approval
is
just
the
beginning.
For
the
most
part
outside
of
Germany,
we
will
not
be
able
to
start
our
promotional
efforts
until
we
have
secured
reimbursement
on
a
country
by
country
basis.
With
that,
I
will
turn
the
call
over
to
Karl.
K
Karl Gubitz
Chief Financial Officer, argenx SE
Thank
you,
Keith.
Slide
13
please.
Our
2021
financial
results
are
detailed
in
your
press
release
from
this
morning.
So
I
will
only
highlight
some
of
the
key
points
here.
We
ended
the
year
with
cash,
cash
equivalents
and
current
financial
assets
at
$32.3
billion.
This
puts
us
in
a
very
strong
position
for
our
first
commercial
launch
and
to
execute
our
plan
in
2022.
Based
on
our
current
plans
to
fund
the
business,
and
assuming
successful
readouts
for
each
of
these
programs,
we
expect
to
utilize
up
to
half
of
our
all
available
cash
this
year.
From
a
utilization
perspective,
we
think
about
in
the
following
way.
First,
R&D
and
our
ongoing
clinical
trials,
we
will
be
in
10
efgartigimod
indications
by
the
end
of
the
year
and
do
two ARGX-117
indications.
So
our
development
continues
to
be
the
largest
proportion
of
our
spend.
Second,
our
inventory
build
and
supply
chain
to
support
our
global
launch
and
global
trials,
we
are
building
for
success
to
ensure
continuity
of
drug
supply
to
patients.
Third,
the
infrastructure
of
our
global
launch,
first
in
the
US,
then
Japan,
Europe
and
Canada.
And
finally,
our
continued
investment
in
our
discovery
engine
and
the
expansion
of
our
pipeline
through
our
immunology
innovation
program.
For
the
full
year
2021,
we
had
total
revenues
of
$497.3
million.
A
large
majority
of
this
was
due
to
income
from
collaboration's
primarily
– primarily
but
one-time
recognition
of
$315.1
million
following
the
termination
of
a
Janssen
collaboration
agreement,
and
our
cost sharing
and
milestone
payments
from
Zai
Lab
totaling
$177.5
million.
There
were
no
product
revenues
in
2021.
Other
operating
income
was
$42.1
million.
In
2021,
our
total
R&D
expenses
was
$580.5
million,
and
our
SG&A
expenses
was
$307.6
million.
As
I
mentioned
at
the
start,
you
can
find
additional
details
behind
these
numbers
in
the
press
release
we
issued
this
morning.
I'll now turn the call back to Tim.
T
Tim Van Hauwermeiren
Thanks,
Karl.
Before
I
conclude,
I'd
like
to
call
out
a
few
personal
updates.
You
saw
in
our
press
release
that
Yvonne
Greenstreet
will
be
leaving
our
board
following
her
promotion
to
CEO
at
Alnylam.
We
are
very
excited
for
Yvonne
and
want
to
express
our
gratitude
for
the
contributions
she
made
as
a
board
member.
We
also
announced
the
appointment
of
Malini
Moorthy,
the
General
Counsel
at
argenx.
This
was
a
planned
transition
and
aligns
closely
with
our
evolution
to
a
commercial
company.
Malini
has
worked
in
large
commercial
organizations
for
almost
two
decades
and
has
the
perfect
experience
to
help
us
navigate
this
new
stage
of
our
development.
And
finally,
we
are
nearing
April
the
1st
and
our
planned
CMO
transition
from
Wim
Parys
to
Luc
Truyen.
Wim
has
transformed
our
development
organization
over
the
past
three
years.
So
we
are
grateful
that
he
will
continue
with
argenx
as
an
advisor
on
our
board's
R&D
committee.
Luc
joined
argenx
six
months
ago
from
J&J
and
brings
significant
development
experience
in
the
neuromuscular
space.
We
are
excited
to
have
him
in
this
leadership
role.
Last
year
was a
remarkable
year
for
the
company
and
we're
off
to
a
great
start
in
2022.
Slide
14.
We
have
two
near-term
data
readouts,
first
ADAPT
subcu
this
month
and
then
ADVANCE
and
ITP
in
the
second
quarter.
By
the
end
of
the
first
quarter
of
2023,
we
also
expect
top
line
data
from
our
CIDP
trial
and
our
second
trial
in
ITP.
So
we're
not
short
of
upcoming
catalysts.
We
announced
in
our
press
release
this
morning
that
the
timing
of
the
top
line
data
from
the
pemphigus
trial
is
currently
under
review
in
light
of
the
geopolitical
situation
in
Ukraine.
While
exposure
is
limited
given
the
global
nature
of
the
trial,
we
cannot
reiterate
our
timelines
until
we
have
time
to
assess
the
situation
more
closely.
The BALLAD
trial
of
efgartigimod
and
BP
started
late
last
year
and
IQVIA in
myositis
will
start
imminently.
We
also
announced
four
new
efgartigimod
indications
that
we
will
start
evaluating
this
year,
including Sjogren's
and
COVID-19
mediated
parts
through
our
collaboration
with
IQVIA
and
membranous
nephropathy
and
lupus
nephritis
through
our
collaboration
with
Zai.
ARGX-117
is
now
in
our
first
patient
study
in
MMN,
and
we
are
excited
to
launch
a
trial
in
delayed
graft
function
later
this
year.
You
can
see
how
our
kidney
franchise
is
taking
shape.
Overall,
we
are
planning
for
success
and
building
up
commercial
franchises
that
will
enable
us
to
have
economies
of
scale
as
we
prepare
for
future
launches.
And
we
would not
be
argenx
if
we
did
not
continue
to
invest
in
our
science.
Slide
15.
We
will
be
advancing
ARGX-119
into
a
Phase
1
trial
after
our
CTAs
filed
later
this
year
and
through
our
IAP
there
are
more
programs
to
come.
Before
we
open
the
call
for
questions,
I
really
want
to
applaud
our
field
teams.
I
have
been
on
the
road
with
them
and
I'm
very
impressed.
It
is
thanks
to
their
teamwork
and
dedication
that
we
have
a
strong
start
to
our
launch,
[ph]
we
shared (00:24:05)
the
state
of
our
launch
in
these
early
days
and
we
look
forward
to
sharing
more
in
May.
Mostly,
I'm
excited
to
finally
be
reaching
patients
and
bringing
them
in
new
treatment
option.
This
is
honoring
a
commitment
we
have
long
made
to
the
gMG
community.
Thank
you
all
for
the
time
today.
We
will
now
take
your
questions.
[Operator Instructions]
Operator
Your
first
question
comes
from
the line
of
Derek
Archila
from
Wells
Fargo.
Your
line
is
open.
D
Derek Archila
Analyst, Wells Fargo Securities LLC
Hey,
good
morning,
guys,
and
congrats
on
the
progress.
Just
two
quick
questions
from
us,
I
guess, first,
based
on
what
you
guys
are
seeing
and
hearing
on
the
VYVGART
launch
and
myasthenia
gravis,
I
guess
are
you
still
pretty
comfortable
where
consensus
estimates
are
right
now?
And
then
just
a
quick
follow-up
on
the
ITP
study
that's
expected
in
the
second
quarter. Maybe
you
can
just
kind
of
frame
out
for
us
what
your
expectations
are
there
in
terms
of
the
primary
endpoint
and
where do
you
see
the
market
opportunity
for
efgartigimod
in
ITP?
Thanks.
K
Karl Gubitz
Chief Financial Officer, argenx SE
Hello,
Derek.
Thank
you
for
your
question.
In
terms
of
revenue
projections,
we
are
not
going
to comment
on
the
revenue
projections
at
the
moment.
We
don't
we're
not
providing
our
own
forecast.
It
really
is
too
early
in
the
launch,
and
we
will
provide
guidance
later
on.
In
terms
of
analysts'
consensus,
as
you
know,
but
the
numbers
are
$97
million
for
the
full
year
for
US
revenues
and
$6
million
for
the
quarter.
Those
are
the
analysts'
consensus,
and
we
are
increasingly
comfortable
with
those
numbers.
T
Tim Van Hauwermeiren
So
on the
second
question,
Derek,
and
thank
you
for
joining
us
today.
Remember
what
we
learned
in
the
Phase
2
clinical
trial,
but
also
what
we
could
see
in
other
ITP
trials
that
is
a
significant
placebo
effect
going
on
in
ITP
patients.
So
the
primary
endpoint
is
a
very
tough
endpoint.
It's an
endpoint
designed
to
completely
control
placebo,
having
in
four
out
of
six
consecutive
visits,
a
platelets
count
of
kind
of
50,000 platelets per
microliter
is
a
very
tall
bar.
So
the
primary
endpoint
is
really
designed
to
create
a
statistically
significant
delta
between
active
and
placebo.
The
full
color
on
the
qualities
of
the
molecule
in
ITP
and
its
potential
to
have
a
competitive
position
there
will
really
come
from
the
secondary
endpoints
where
we
will
study
things
like
cumulative
platelet
counts,
total
platelet
counts
of
the
period,
bleeding
effects,
quality
of
life
and
the
like.
And
that
should
basically
tell
us
where
we
could
fit
in
a
treatment
paradigm.
Maybe,
Keith,
you
can
comment
briefly
on
how
we
look
at
the
opportunity.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah.
So,
Derek,
as
far
as
the
market
opportunity,
I
guess
I
would
call
out
the
TPO's
themselves
are
doing
more
than
$2
billion
in
revenue
a
year
globally.
And
really,
where
we
feel
the
opportunity
is,
is
we're
not going
to
displace
TPO.
We
would
like
to
play,
as
Tim
said
in
the
prepared
remarks,
right
after
the
first
TPO.
So
about
60%
of
patients
respond
to
TPO
and
about
50%
of
them
are
going
to
then
relapse.
That's
where
we
feel
that
efgartigimod
can
potentially
play
into
it
because
of
its
impact
on
the
disease
from
multiple
mechanisms
of
action.
So
it's
not
just
about
–
it's
not
just
about
creating
more
platelets.
It's
also
about
managing
the
clearance,
the
function
of
the
platelets.
So,
it
should
be
a
better
option
than
patients
rotating
for
one,
two
or
three
TPOs.
D
Derek Archila
Analyst, Wells Fargo Securities LLC
Got
it.
Thanks,
guys.
Operator
Your
next
question
comes
from
the line
of
Tazeen
Ahmad
from
Bank
of
America.
Your
line
is
open.
T
Tazeen Ahmad
Analyst, BofA Securities, Inc.
Hi, guys.
Good
morning.
Thanks
for
taking
my
question.
Just
a
clarification
one
for
the
upcoming
subcu
dataset
that's
due
this
quarter, assuming
that
the
data
shows
what
you
wanted
to
show,
can
you
just
walk
us
through
what
the
next
steps
would
be
in
terms
of
going
to
FDA?
And
when
you
think
you
could
file
for
what
I'm
assuming
would
be
an
FNDA?
Just
to
clarify
that.
Thank
you.
Or
an
FBLA?
T
Tim Van Hauwermeiren
Hi Tazeen,
this
is
Tim
speaking.
Thanks
for
joining
us
today
and
thank
you
for
your
question.
So,
in
the
United
States
specifically,
the
situation
with
the
FDA
is
that
the
subcu
product,
which
is
in
combination
with
the Halozyme's
ENHANZE technology,
is
considered
to
be
a
separate
product.
So,
this
is
not
going
to
be
an
FBLA.
It
will
be
its
own
BLA.
Therefore,
we
think
it's
also
its
own
distinct
product
presentation
we
will
be
able
to
position
in
the
marketplace.
Now,
that's
great
news
from
a
commercial
point
of
view.
From
a
workstream
point
of
view
to
its
submission,
we
still
anticipate
that
we
will
be
able
to
reuse
big
sections
of
the
IVBLA
really
into
that dedicated
subcu
BLA.
Thanks
for
the
question.
Operator
Your
next
question
comes
from
the line
of
Akash
Tewari
from
Jefferies.
Your
line
is
open.
A
Akash Tewari
Analyst, Jefferies LLC
Hey,
guys.
So,
a,
the
bolus
of
response
that
you
mentioned,
what
percent
of
early
scripts
have
been
these
ultra-refractory
patients
and
is
there
any
color you
can
give
us
on
sizing
up
that
market
opportunity?
Are
we
talking
about
a
1,000, 2,000 patients
here
or
something
more?
And
then
maybe
on
the
Principia
of
BTK,
which
misses
primary
and
secondary
endpoint
in
pemphigus,
Sanofi
hinted
that
was
due
to
the
high
placebo
response
given
the
placebo
arm
also
received
steroids?
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah,
I'll
take
the
first
question.
So,
Akash,
in
regard
to
what
we
referenced
in
the
prepared
remarks
–
did
we
lose?
Operator
No.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Okay.
Akash,
in
response
to
the
severe
relapse –
relapsed
refractory
that
we've
seen
start
in
so
far
in
this
first
eight
weeks,
I
think
it
was
a
little
bit
of
a
surprise.
These
are
patients
that
have
experienced
really
all
other
therapies
that
are
available,
including and up to
C5
and
they
have
not
responded.
And
so
they
have
come
on
to
VYVGART.
So
I
think
that
was
a
little
bit
of
pent-up
demand
that
was
a
surprise
to
us.
The
question
is,
is
this
just
going to
be
in
the
early
days
because
these
are
the
patients
that
have
had
no
success
with
any
other
therapy?
A
Akash Tewari
Analyst, Jefferies LLC
Okay.
Sorry.
Can
you guys
hear
me?
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yes.
T
Tim Van Hauwermeiren
Yeah.
A
Akash Tewari
Analyst, Jefferies LLC
Okay.
Sorry
about
that.
So
look
on
the
Sanofi,
the
BTK
failing
in
pemphigus.
Can
you
just
comment
on
in
the
primary
endpoint
patients
in
the
placebo
arm
got
tapered
down
to
minimal
steroids?
They
didn't
go
completely
off
the
drug. Do
you
feel
like
that's
a
risk
for
your
studies,
given
it
looks
like
steroids
in
combination
with
VYVGART
was
kind
of
driving
some of
the
complete
responses
in
your
Phase
2
data?
Thank
you.
T
Tim Van Hauwermeiren
Thank
you, Akash.
So
difficult
for
us
to
comment
on,
you
know,
why
the
Phase
3
trial
of
Principia
failed.
Mind
you,
they
failed
over
the
entire
line,
right?
Not
just
the
primary
endpoint,
but
also
the
secondary
endpoints.
I
think
we
did
our
homework
well.
When
we
designed
our
clinical
trial,
we
have
been
talking
to
typically
those
KOLs,
who
were
deeply
involved
in
pemphigus
trials,
including
the
Principia
trail and
rituximab
trial.
So
we
think
we
have
been
avoiding
some
of
the
classical
pitfalls in
clinical
trial
design
in
pemphigus.
We
are
in
a
steroid
taping
protocol
that
is
a
notoriously
difficult
protocol,
but
we're
on
top
of
it,
so
we
carefully
monitor
the
steroid
tapering.
So
that
goes
according
to
protocol.
Mind
you,
that
the
mode
of
action
between
the
BTK
inhibitor
and
efgartigimod
are
totally
different
right,
I
mean,
we're
not
impacting
a
B
cell
repertoire,
hoping
to
see
a
downstream
effect
on
allergies
and
disease
states.
We're
really
hitting
the
disease
biology
in
its
heart.
So
we
have
pretty
exciting
data
from
the
Phase
2
study
that
if
you
eliminate
these
pathogenic
IgGs,
you
can
put
patients
into
a
complete
remission,
actually,
a
number
of
them
very
durable
remissions.
And
stay
tuned,
I
think
at
the
upcoming
[ph]
SSID (00:32:31)
conference
later
this
year,
we
will
continue
to
show
very
strong
data
for
our
molecule
in
pemphigus.
Thanks
for
the
question.
Operator
Your
next
question
comes
from
the line
of
Yaron
Werber
from
Cowen.
Your
line
is
open.
Y
Yaron Werber
Analyst, Cowen & Co. LLC
Great,
thanks
for
taking
my
question.
I
got
an
inter-related
question
on
the
upcoming
data
for
ADAPT
subcu.
We're
getting
a
lot
of
questions
on
it.
Perhaps
the
first
one,
the
– you've
over
enrolled
that
study. So
could
you
– disclose
closed the
enrollment
with 111
patients
or
so,
you
only
needed
50
really
to
support
the
BLA
filing.
Are
all
111
going
to be
included
in
the
primary
and
the
secondary
endpoints?
That's
the
first
question
at
day
29,
and
IgG
reduction.
And
then
secondly,
for
the
secondary
endpoints
on
MG-ADL,
and
which
you're
looking
at
a
12
weeks,
are
you
going
to
–
do
you
think
you're
statistically
powered
now
with
111
patient
to show a
difference.
Thank
you.
T
Tim Van Hauwermeiren
Thanks,
Yaron.
I'm happy
we
can
clarify
this.
So
there
are
two
objectives
we
need
to
meet
right
in
this
study.
First
is
we
need
to
hit
the
primary
endpoint
which
is
all
about
demonstrating
non-inferiority
between
IV and
subcu
and
in
order
to
do
that,
we
believe
that
with
50
patients
we
sufficiently
powered.
Now
the
second
objective
we
need
to
meet
is
to
basically
collect
the
minimum
database
size
which
we
require
for
this
separate
BLA
submission.
And
in
that
context,
you
need
to
see
what
you
called
it
all
recruitment
111
patients.
These
patients,
together
with
the
patients
to
be rolled
over
from
the
open
label
extension
study
from
IV
to
subcu
together
will
be
a
sufficient
number
of
patients
and
to
go
into
the
safety
database.
So
once
we
have
both
data
points,
the
primary
endpoint
and
the
safety
data
point,
we
will
be
able
to
go
into
submission.
On
the
secondary
endpoints
in
the
trial,
yes,
we
are
collecting
information
on
the
ADL
and
QMG,
but
this
will
be
more
qualitative
information
because
you're
right.
This
study
is
only
powered
to
hit
its
primary
endpoint.
We
are
collecting,
of
course,
further
color
and
evidence
from
both
the
ADL and
the
QMG
score,
but
it's
all
about
showing
a
non-inferior
IgG
reduction.
Thank
you
for
the
question.
Operator
Your
next
question
comes
from
the line
of
Joon
Lee
from
Truist
Securities.
Your
line
is
open.
J
Joon Lee
Analyst, Truist Securities, Inc.
Hi.
Thanks
for
taking
our
questions
and
congrats
on
all
the
progress.
Is
ADDRESS
study
for
pemphigus
the
only
study
that's
exposed
to
Eastern
European
sites
including
Ukraine
or
your
other
studies
such
as ADVANCE
or
ADHERE
also
enroll
from
Ukrainian
sites,
but
maybe
not
impacted
due
to
the
broader
geographic
enrollment?
And
I
have
a
quick
follow-up.
Thank
you.
T
Tim Van Hauwermeiren
Thank
you,
Joon.
So
all of
our
trials,
by
definition,
are
global
trials.
So
these
are
all
rare
indications
that
all
spread
over
the
globe,
and
that
turns
out
to
be
a
strength.
When
things
hit
you
like
COVID,
a
COVID
pandemic
or
in
this
case,
a
geopolitical
issue,
so
exposure
is
always
going to
be
relatively
limited
to
whatever
study
you're
talking
about.
For pemphigus,
we're
in
a
slightly
different
position
because
our
incidence
and
prevalence
is
a
little
bit
tied
to
geography.
I
mean,
you
see
different
pockets
of
patients
and
therefore,
we
have
a
slightly
higher
exposure
in
Ukraine
and
Russia
and
that's
also
why
we
felt
compelled
to
give
you
a
heads
up
on
the
data
readout
for pemphigus.
In
the
ITP
subcu
and
the
CIDP
study,
exposure
is
minimal,
and
we
have
time
to
rebalance
without
having
to
change
anything
concerning
timelines.
For pemphigus, we
are
currently
going
through
the
risk
analysis,
and
we
will
be
able
to
give
you
an
update,
probably
in
the
next
quarterly
earnings
call.
J
Joon Lee
Analyst, Truist Securities, Inc.
Great.
T
Tim Van Hauwermeiren
Please,
your
second
question.
J
Joon Lee
Analyst, Truist Securities, Inc.
Yes,
you
have
a
lot
of
trials
underway,
which
is
obviously
reflected
in
your
R&D
spend.
Hopefully,
many
will
succeed,
but
it's
unlikely
that
all
will
succeed,
similar
to
what
happened
with
the
[indiscernible]
(00:36:42)
population.
So
do
you
have
any
plans
to
partner
with
an
AI
company
to
analyze
the
rich
clinical
dataset
that you're
generating
and
to
identify
certain
biological
signatures
to
improve
the
odds
of
your
clinical
success
and
we're
just
asking
because
we've
been
talking
to
a
lot
of
AI
companies
with
autoimmune
focus
and
reducing
clinical
risks
using
AI
seems
to
be
the
focus
of
many
companies
and
just
curious
your
thoughts
on
that,
since
you
have
a
lot
of
trials
ongoing.
Thank
you.
T
Tim Van Hauwermeiren
It's
a
great
question,
Joon
and
whilst
we're
not
deeply
engaged
within
AI,
we
are
following
similar
strategies.
So
first
of
all,
these
are
all
rare
diseases
and
there
are
not
too
many
precedent
trials
out
there
or
too
many
data
you
could
mine
in
an
intelligent
way.
That
is
a
challenge.
So
we
do
talk
to
experts
extensively
when
we
design
our
clinical
trials
trying
to
make
the
studies
as
diverse
as
possible
when
it
comes
to
inclusion
exclusion
criteria.
Also, when
it
comes
to
our
go/no-go
decision
points
somewhere
in
these
trials
where
you
have
the
ability,
for
example,
to
further
tweak
certain
aspects
of
the
registrational
part
of
the
studies.
Similar
to
what
we
did
in
CIDP,
we're
doing
that
in
BP
trial.
We're
doing
that
in
the
basket
trial
in
myositis.
So
I
think
we
find
our
ways
to
risk
mitigate
these
studies
in
an
intelligent
way.
Still
I
think
I'd
like
to
comment,
these
are
still
clinical
experiments,
which
all
have
their
own
intrinsic
risks
associated.
Thanks
for
the
question.
Operator
Your
next
question
comes
from
the line
of
Yatin
Suneja
from
Guggenheim
Partners.
Your
line
is
open.
Y
Yatin Suneja
Analyst, Guggenheim Securities LLC
Hey,
guys,
thank
you
for
taking
my
question.
So
question
is
on
the
patient
population,
so
when
you
talk
about
the
17,000
the
gMG
patients
that
you
are
targeting,
can
you
maybe
help
us
subcategories
these
patients.
It
is
our
understanding
that
there
are
different
categories
within
these
17,000,
and
some
might
be
more
or
might
be
easier
patient
to
get
early in
the
launch curve,
like
patients
who
are
on
chronic
IVIg,
maybe
Soliris
non-responder.
So
if
you
can
just
give
us
a
flavor
of
what
exactly
you
are
seeing
in
these
buckets,
how
big
are
these
buckets,
and
how
should
we
expect
some
of
these
buckets
that
are
maybe
first
to
come
to
your
therapy.
So
that's the
first
question.
And
the
second
one
and
last
right
now
is
on
the
J
code,
can
you
also
talk
about
what
a
limitation
it
might
be
having,
if
any,
at
this
point
and
how
that
dynamic
would
change
once
you
once
you
get
it
in
Q3,
so
two
questions
for
me.
Thanks.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Great.
Well,
thank
you for
the
question,
Yatin.
First
of
all,
what
I'd
say
is
the
patient
population
that
we
are
seeing
that
is
adapting
VYVGART
in
this
early
period,
this
first
eight
weeks
is
really
aligned
with
the
ADAPT
trial.
It
is
really
across
the
treatment
spectrum.
As
I
mentioned,
we
are
getting
some
relapsed
refractory
patients.
We've
also
had
some
from
IVIg.
But
typically
when
you
look
at
that
target
population
of 17,000,
these
are
patients
that
have
tried
[ph]
myasthenia
(00:39:56)
many
times
they've
had
a
steroid
added
and
many
of
them
have
also
gone
on
an
off
label
broad
IST.
And
we
have
seen
each
of
those
types
of
patients
experience
VYVGART
in
the
early
stages
of
the
launch.
As
far
as
your
second
question
on
the
J
code
and
the
limitations,
what
the J
code
basically
does,
it's
in
the
buy-and-bill
situation
and
it
is
putting
more
work
on
the
office
to
get
reimbursed.
It's
not
that
it
makes
it
where
it
cannot
be
reimbursed
because
we
are
having
product
reimbursed
in
buy-and-bill
setting.
It
just
may
add
an
extra
step
of
going
through
an
appeal
process,
and
it
puts
more
work
on
the
office
staff.
You
also
have
a
limited
number
of
offices
that
actually
elect
not
to
prescribe
a
product,
why
they
don't
have
a
J
code
because
they
don't
want
to put
the
extra
work
on
the
office.
I
think
the
last
thing
that
we
need
to
remember
is
unlike
an
oncology
setting,
your
buy-and-bill
market
in
neurology
is
smaller
than
what
you
see
in
[indiscernible]
(00:40:56) and
it's
really
in
that
buy-and-bill
where
you
see
the
J
code
impact.
But
we
expect
to
have
our
own
individualized
J
code
in
quarter
three.
Operator
Your
next
question
comes
from
the
line
of
James
Gordon
from
JPMorgan.
Your
line
is
open.
J
James D. Gordon
Analyst, JPMorgan Securities Plc
Hello,
James
Gordon, JPMorgan. Thanks
for
taking
the
questions.
The
first
question
was
just,
so
with
regard
to
MG.
How
important
do you
think
first
mover
status
is
and
formulation
relative
to
other FcRns
in
MG?
And
I
also
want
to
ask whether
UCB are going to present their roza FcRn
Phase
3
data
at
ALL
next
month.
And
they
talked
very
confidently about
how
they're going
to
present
data
that
shows
it's
very
competitive versus VYVGART.
So,
do
you
think
there
are
areas
where
they
could
actually be
competitive
or
given
the
first
mover
advantage
formulation
of
other
aspects,
et
cetera?
Other
areas
where
there
could
be
a
risk
factor?
How
are
you
feeling
about
that
? The
first
question.
I'll
ask
a
follow-up
now,
which
was
just
on
Russia-Ukraine
disruption,
and
I
think
the
comment
on
PV
and
potential
delays
there.
But
the
ITP
subcu
trial
looks like
it's
got
quite
a
lot of rush inside.
And
I
think
about
a
third of
the
sites
that
are
out
there
in
Russia.
So
is
there
a
risk
that
that
study
is
also
going
to
be
disrupted
and
delayed?
Or
is
it
more
of
an issue
if
it's
Ukraine
versus
Russia?
T
Tim Van Hauwermeiren
Yeah.
Let me
start with
the
second
question
first,
and
I'm
happy
to
hand
over
to
Keith
to
talk
about
our
competitive
position
in
the
MG
landscape.
It's
still
just
about
the
sites
which
you
can
see
on
clinicaltrials.gov,
but
it's
about
the
actual
number
of
patients
which
actually
have
been
enrolled
through
this
sites.
So,
when
we
look
at
the
real
situation,
which
is
actual
number
of
patients,
we
feel
that
the
subcu
study
for
efgartigimod
in
ITP
is
perfectly
under
control,
I
would
say
that
indeed
there
is
somewhat
more
exposure
in
the
pemphigus
trial.
So,
maybe
we
will
have
to
overcompensate that
in
some
of
the
sites
that
is
analysis
which
is
ongoing.
And
so,
I
don't
think
there's
any
reason
to
change
the
guidance
on
readouts
timing
for
the
ITP
subcu
custody
or
the
CIDP
subcu
custody.
Maybe
Keith
you
want
to
comment
on
how
we
look
at
our
competitive
position
in
the
MG
landscape.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Sure.
So
James,
first
of
all,
I
think
it's
premature
to
comment
anything
on
the
Phase
3
data
because
we
haven't
seen
any
specific
data
at
all.
As far
as
the first
mover advantage,
I
think
that the
opportunity
that
exists
with
VYVGART
is
based
on
the
data
itself.
Let
start
with the
efficacy.
Between
the
first
and
second
cycle
almost
8
out
of
every
10 patients
that
experienced
VYVGART
are
going
to
have
a
clinically
meaningful
response.
We
also
have
a
very
rapid
onset
of
action
with
84%
of
them
responding
within
the
first
two
weeks
and
the
minimal
symptom
expression,
sending
these
patients
to
where
they
have
no
symptoms
at
all.
Right
now,
it's
the
highest
number
that's
been
recorded
in
a
clinical
trial.
Secondly,
take
a
look
at
the
package
insert
that
we
have.
It
is
very
clean.
The
safety
profile,
this
is
one
of
the
things
that
we're
hearing
from
the
physicians
that
are
prescribing.
They're
impressed
about
this.
There's
no
premeditation.
There's
no
black
box
warning
and
the
safety
is
riding
up
through
all
of
our
studies.
The
last
thing
I
would
say
is
individualized
dosing.
We
are
providing
convenience
to
patients
when
they
can
take
advantage
of
the
individualized
dosing.
And
so
I
guess
what
I
would
say
is
we've
set
the
bar
high,
but
let's
wait
and
see
data.
Operator
Your
next
question
comes
from
the line
of
Matthew
Harrison
from
Morgan
Stanley.
Your
line
is
open.
M
Matthew Harrison
Analyst, Morgan Stanley & Co. LLC
Great.
Good
morning. Thanks
for
taking
the
questions.
I
guess
two
for
me.
One,
I don't
know
if
you're
willing,
but
it
would
be
interesting
to
hear
what
you're
sort
of
seeing
on
a
month
over
month
basis?
Are
you
seeing
patients
accelerate
or
not?
Just
so
we
can
get
some
sense
of
how
you're
thinking
about
the
bolus.
And
then
second
question,
just
because
I
think
a
lot
of
us
haven't
seen
a
Japan
launch
before.
Can
you
give
us
some
sense
of
whether
or
not
you
think
Japan
can be
a
meaningful
contributor
this
year?
And
just
given
the
commentary
around
when
you
get
the
price,
but
the
fact
that
it
sounds
like
you
can
already
start
to
line
up
patients?
Thanks
very
much.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah.
Hey,
Matthew.
Thanks,
thanks
very
much
for
the
question.
So
as
far
as
what
we're
seeing
on
a
month
over
month
basis,
we've
only
had
eight
weeks.
So
it's
really
tough
to
give
you
a
month
over
month
basis.
I
can
tell
you
that
we're
– what
we're
seeing
in
patient
demand,
it's
been
gradual,
and
it's
been
consistent.
I
think
that
we
have
prepared
well
in
ADVANCE
on
each
of
those
strategic
imperatives.
And
I
think
the
team
is
out
there
executing
on
each
of
the
areas,
whether
it's
the
patient
awareness,
the
healthcare
professionals
or
the
payers.
I'm
also
really
pleased
with
the
progress
that
we
have
through
My
VYVGART
Path,
because
when
you
have
a
brand
new
first
in
class
product
with
a
brand
new
mechanism
of
action,
there
does
take
some
pull
through
to
turn
demand
into
actual
infused
patients.
So
we
can
talk
a
little
bit
more
about
patient
trends
when
we
actually
get
to
a
first
quarter
earnings
call.
As
far
as your
second
question
about
the
Japan
launch,
again,
I'm
going to
advise
on
a
very
gradual,
consistent
growth
because
we
run
into
the
same
issue
that
exists
in
the
United
States
and
that
is
education
on
a
first
ever
mechanism
of
action.
And
also,
I
would
call
out
to
you
that
the
number
of
clinical
trial
sites
that
we
had
in
Japan
is
smaller
than
what
we
even
experienced
in
the
US.
So
I
wouldn't
think
of
you
have
a
bolus
of
patients
that
are
set
to
go.
Now
one
thing
that
we
do
have
different
in
Japan,
I
remind
you
that
in
the
approval
that
we
received
in
January,
the
Japan
label
will
include
zero
negative
patients.
Operator
Your
next
question
comes
from the
line
of
Allison
Bratzel
from
Piper
Sandler.
Your
line
is
open.
A
Allison M. Bratzel
Analyst, Piper Sandler & Co.
Hi,
good
morning.
Thank
you
for
taking
the
question.
So
just
one
on
the
source
of
the
[ph]
patients, (00:46:57)
having
sat through
some
of
the gMG
patient
webinars
about VYVGART.
It
seems
like
there's
definite
interest
not
just
in
switching
from
IVIg,
but
surprisingly
in
switching
from
Soliris
as
well,
so
I
know
it's
early
days,
but
does
that
match,
what
you're
seeing
in
the
field?
And
then
I
guess
just
to
the
extent
that
you
are
seeing
patients
having
an
interest
in
switching
from
Soliris
to
VYVGART,
what's
the
primary
driver
or
reason
behind
that
from
a
patient
and neurologist
point
of
view
and
just
how
do you
expect
that
dynamic
to
evolve
when
Ultomiris
gets
a
gMG
label
mid-year?
Thanks.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah. So
thank
you
for
the
question,
Allison.
I
guess
the
first
thing
that
I
would
say
is
it's
too
early
to
predict
a
trend,
because
we're
talking
about
individual
patients.
And
as
you
know,
in
rare
disease,
every
single
patient
is
different.
And
we
also
know
just
from
the
data
that
you're
not
going
to
get
every
single
patient
to
respond
to
a
therapy.
You
can
go
back
and
look
at
the
REGAIN
study
or
the
data
that
was
released
on
Ultomiris.
So
regardless
of
what
product
the
patient
has
gone
on,
you're
going
to have
a
part
of
that
population
that
is
not
going
to
respond.
And
when
they
have
not
responded,
they're
going
to
look
for
other
options.
And
that's
what's
happened
with
VYVGART
becoming
another
tool
to
place
in
the
box
of
the
healthcare
professionals.
Operator
Your
next
question
comes
from the
line
of
Douglas
Tsao
from
H.C.
Wainwright.
Your
line
is
open.
D
Douglas Tsao
Analyst, H. C. Wainwright & Co. LLC
Hi,
good
morning
and
thanks
for
taking
the
questions.
I'm
just
curious
on
the
ADAPT
NXT
trial,
did
you
start
that
sort
of
based
on
any
sort
of
questions
from
providers
to
provide
clarity
in
terms
of
the
sort
of
dosing
regimens
and
have
you
gotten
an
early
sense
about
how
physicians
are
going
to
implement
the
individualized
dosing
that
you
have
in
the
label?
Thank
you.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah.
So
Douglas, we
have
been
working
with
a
group
of
KOLs
for
better
than
two
years
now.
It's
been
since
the
Phase
2
data
that
we
discuss
the
concept
of
individualized
dosing.
It
first
came
from
the
patients
when
we
shared
with
them
the
Phase
2
data,
and
they
love
the
idea
of
the
cycles,
and
they
love
the
idea
of
having
the
time
off
therapy.
We
then
went
and
discussed
this
with
the
KOLs,
and
they've
seen
the
data
and
they're
very
pleased
with
it.
The
question
that
they
had
is
what
if
I
require
somebody
that
might
need
a
little
bit
more
consistent
dosing?
And
what
we
always
aim
to
do
is
to
be
able
to
have
data
based
answers,
and
that's
basically
what
this
trial
has
been
set
up
for.
T
Tim Van Hauwermeiren
I
think
the
other
way
to
look
at
this
is,
look,
we
have
a
long
term
commitment
to
the
MG
space
and
what
we
want
to
offer
MG
patients
around
the
globe
is
the
most
complete
offering
and
the
way
you
have
to
understand
the
most
complete
offering
is
maximum
flexibility
from
a
dosing
point
of
view.
This
is
a
snowflake
disease.
Every
MG
patient
is
different.
You
cannot
basically
take
them
to
the
same
standard
approach.
And
we
also
want
to
have
flexibility
from
a
product
presentation
point
of
view.
There
are
different
preferences
and
needs
out there
in
the
market
for
both
an
IV
product
and
a
subcu
products.
So
look
at
it
through
this
lens.
D
Douglas Tsao
Analyst, H. C. Wainwright & Co. LLC
Okay.
Great.
And
again,
one
follow-up.
Just
in
the
early
days,
have
you
had
any
sort
of
color
on
how
docs
are
implementing
with the
individualized
dosing?
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah. So
I
mean,
first
of
all,
they
like
the
idea
of
the
individualized
dosing.
They
like
the
idea
of
only
treating
a
patient
when
they
need
therapy.
They
also
like
the
idea
of
the
data
that
they've
seen
in
what
percentage
of
patients.
As
you
know,
during
the
launch,
we
shared
with
you
that
58%
of
patients
require
five
cycles
or
fewer.
The
questions
that
they've
had
is
how
should
they
start
the
patient
and
how
do I
figure
out,
how
to
get
the
individualized
dose
that
my
patient
needs?
And
a
lot
of
them
have
taken
a
look
at
how
they
utilizes
off-label
IVIG
to
treat
MG,
and
that
is
basically
let's
get
our
patient
into
response
and
get
that
patient
to
the
maximum
response
that
we
can
have.
And
then
as
we
have
the
patient
in
response
based
on
the
label,
it's
their
clinical
evaluation
and
their
discussion
with
the
patient
on
how
they
stretch
that
interval
out.
And
that's
what
we've
seen
happen
in
the
open
label
extension,
and
that's
what
we'll
see
happen
in
the
real
world.
Operator
Your
next
question
comes
from
the line
of
Danielle
Brill
from
Raymond
James.
Your
line
is
open.
D
Danielle Brill
Analyst, Raymond James & Associates, Inc.
Hi,
guys,
good
morning.
Congrats
on
the
progress
and
thanks
so
much
for
the
questions.
I
have
a
couple
on
ITP.
Can
you
mention
placebo
responses
are
common,
but
I
believe
the
placebo
response
rate
was
actually
pretty
low
in
[ph]
Rigel's (00:51:53)
program,
are
there
specific
differences
in
the
population
[ph]
they
enrolled
versus (00:51:57)
those
in
ADVANCE
that
might
explain
this?
And
then
in
their
Phase
3
publication
they
showed
efficacy
was
much
lower
in
patients
who
are
antibody
negative.
I'm
just
wondering
how
we
should
think
about
potential
risk
of
including
antibody
negative
patients
in
ADVANCE.
Thank
you.
T
Tim Van Hauwermeiren
Thank
you, Danielle. [Technical Difficulty] (00:52:15)
some
questions.
So
first
of
all,
the
reason
the
placebo
response
was
low
in
the
[ph] Rachel (00:52:19)
trial
is
because
they
basically
have
used
a
similar
endpoint
as
the
one
we're
using.
So
we
have
been
studying
that
trial
in
detail.
They
also
had
an
adjustable
platelet
response
requirement.
So
unlike
the
PPO
registration
trials
where
after a
certain period of
treatment,
it
was
sufficient
to
be
at
50,000
platelets
are
higher
on
a
specific
day.
They
built
in
the
durability
requirement,
and
you
can
indeed
see
how
effective
that
has
been
in
knocking
down
the
placebo.
I
think
in
one
trial
they
had
0%
response.
And
then
in
another
trial,
they
had
something
like
a
1%
response
in
placebo
and
basically
was
trying
to
achieve
similar
numbers
on
placebo
by
applying
similarly
stringent
endpoint.
Now
this
story
on
antibody
negative
patients,
I
don't
think
that
exists.
I
mean
all
ITP
patients.
Primary
ITP
patients
do
have
autoantibodies
styling
the
platelets.
The
issue
is
what
test
you
use
to
analyze
the
antibody
levels
and
what
the
sensitivity
is,
what
the
detection
limit
is
for
these
patients.
So
for
example,
in
our
Phase
2
trial,
we
use
a
more
sophisticated
method
where
we
basically
harvest
platelets,
we
strip
the
autoantibodies
from
the
platelets
and
then
we
semi
quantify
them,
100%
of
the
patients
actually
is
autoantibody
positive.
So
if
you
have
a
true
primary
ITP
patient,
that
patient
will
have
platelet
associated
autoantibodies.
Thank
you
for
the
questions.
Operator
Your
next
question
comes
from
the line
of
Jason
Butler
from
JMP
Securities.
Your
line
is
open.
J
Jason N. Butler
Analyst, JMP Group LLC
Hi,
thanks
for
taking
the
question.
Just
one
from
me
on
reimbursement,
I'm
just
looking
forward
to
the
subcu
products,
given
that
that
products
in
VYVGART
will
be
distinct.
Will
the
value
based
agreements
in
place
for
VYVGART
expand
immediately
on
approval
for
the
subcu subgroup
product?
Or
do
you
need
to
go
through
another
process
because
they're
distinct
products?
And
then
same
question
essentially
for
the
J
code
part of
the
equation,
will
you
need
to
get
a
separate
J
code
for
the
subcu
products?
And
while
you
wait
for
it,
will
the
J
code
you
have
in
place
for
VYVGART
help
in
any
way?
Thanks.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah,
Jason,
thank
you
for
the
questions.
So,
first
of
all,
you
know,
the
work
that
we
did
with
payers
in
ADVANCE
by
putting
them
under
CDA
prior
to
even
having
approval
of
VYVGART.
And
that's
when
we
discussed
all
of
the
data
with
them,
including
what
we
saw
on
the
distribution
on
the
number
of
cycles
per
year,
we
looked
at
the
patient
population.
We
know
that
the
IV
was
weight
based
dose.
And
so
we
really
discussed
them
what
would
make
sense
in
regard
to
a
value-based
agreement
with
them.
We
have
not
yet
made
the
decision
on
exactly
how
we
will
handle
as
we
have
the
approval
for
subcu
but
in
a
true
collaboration
goal
that
we've
had
with
our
IV
launch,
we
will
be
out
with
these
same
payers
in
ADVANCE
of
a
subcu
approval
to
determine
what
will
be
the
best
method
to
take
considering
it
will
be
a
separately
branded
product.
Secondly,
you
asked
the
question
about
the
J
code.
I
think
that
once
you
have
a
subcu
product
that
would
be
available
for
patients
to
give
themself
a
simple
single
injection
at
home,
you're
going
to
see
by
far
the
majority
of
that
subcu
product
acquired
through
specialty
pharmacy.
And
so
that's
not
going
to come
into
play
with
the
J
code
to
the
same
level
that
you're
seeing
with
a
buy
and
bill
infusion
IV
product.
Operator
Your
next
question
comes
from the
line
of
Joel
Beatty
from
Baird.
Your
line
is
open.
J
Joel L. Beatty
Analyst, Robert W. Baird & Co., Inc.
Hi. Thanks
for
taking
the
questions.
First
one
is,
can
you
describe
how
the
patient
experience
has
been
from
the
time
of
prescription
of
VYVGART
to
actually
starting
on
therapy
such
as
what
percent
of
prescriptions
are
being
filled
right
now
and
how
long
it
takes
to
start
on
drug
? Then
the
second
question
is
what
is
the
status
of
VYVGART
being
added
to
treatment
guidelines
for
gMG?
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah, so
first, let's
talk
about
the
experience
from
the
time
that
the
script
was
wrote
to
the
time
that
the
patient
is
infused
and
the
reality
of
it
is
you
have
a
brand
new
product
that's
out
and
available.
And
what
we're
– what
we're
seeing
is
on
a
patient
by
patient
basis.
It
completely
depends
upon
who
their
insurer
is.
What
we
do
know
as
we
don't
have
a
J
code,
as
you've
heard
in
the
prepared
remarks,
the
policies
that
are
being
prepared
by
the
payers,
we
have
about
25%
of
covered
lives
that
have
policies
in
place
right
now.
So
the
process
going
from
demand
to
actual
infusions
in
some
cases
is
longer.
We
expect
this
to
shorten
over
time.
But
I'm
really
proud
of
the
team
at
my
VYVGART
our
nurse
case
managers,
our
case
coordinators
and
our
field
reimbursement
managers
who
are
working
on
every
single
case
to
make
sure
that
we
can
shorten
the
time
to
the
best
of
our
ability.
So
what
was
the
second
question,
please?
J
Joel L. Beatty
Analyst, Robert W. Baird & Co., Inc.
VYVGART
being
incorporated into
treatment
guidelines
for
general.
R
R. Keith Woods
Chief Operating Officer, argenx SE
We're
eight
weeks
into
this
initial
launch
and
really,
it's
too
early
to
say.
Right
now,
the
only
thing
I
can
say
is
the
treatment
guidelines
of
where
we
are
seeing
patients
that
are
being
prescribed.
VYVGART
is
aligned
with
ADAPT,
so
it's
not
necessarily
severe
relapsed
refractory.
In
some
cases,
it's
much
earlier
in
the
treatment
paradigm.
But
I'm
sure
we
will
see
more
treatment
guidelines
over
time
as
the
market
matures.
Operator
Your
next
question
comes
from
the line
of
Manos
Mastorakis
from
Deutsche
Bank.
Your
line
is
open.
M
Manos Mastorakis
Analyst, Deutsche Bank AG
Yes,
hello.
Thank you
for
the question.
So,
yeah,
you
alluded
to
that
already
very
briefly.
But
I
just
want
to
better
understand
your
latest
perspective
on
clinical
differentiation
to
competitors
such
as
[indiscernible]
(00:58:26)
may
be
coming
in
the
future,
as
well
as
competitive
risk
from
broader
use
C5
inhibitors
in
MG
if
Ultomiris
is
approved.
And
a
follow-up
question,
Is
what
would
your
expectations
be
for
the
Phase
3
ITP
data
and
the
clinical
positioning
as
well
in
ITP?
T
Tim Van Hauwermeiren
The
elements we
mentioned.
So
let's
start
with
the
biology,
right.
I
mean,
we're
a
science
based.
We
follow
biology.
Myasthenia
Gravis
is
truly
an
IgG
mediated
disease.
So
the
pathogenic
IgG
antibodies
are
very
well-known.
We
also
know
what
they
do
at
the
neuromuscular
junction
by
binding
acetylcholine
receptors
or
other
building
blocks
of
the
junction.
They
will
basically
prevent
signaling
through
the
acetylcholine
receptors.
They
will
basically
crosslink,
internalize
and
make
the
receptor
unavailable
for
signaling,
and
they
will
also
recruit
components.
So
definitely
complement
this
one
of
the
several
pathogenic
modes
of
action
of
these
autoantibodies.
And
by
nature
of
the
disease
biology,
if
you
clear
the
autoantibody,
you
will
of
course,
eliminate
complement
recruitment
to
the
junction.
But
you
will
also
effectively
take
care
of
the
older
pathogenic
modes
of
action
of
these
autoantibodies.
So
with
upstream
of
any
complement
blocker.
And
I
think
we
have
a
more
complete
blockade
of
the
disease
biology
in
the
pinnacle
of
data
support
that
has
got
taken
what
has
shown
the
highest
ever
clinical
efficacy
in
any
clinical
trial.
What
about
the
differentiation
within
the
FcRn
class?
I
think
it's
extremely
important.
You
guys
remember
that
not
all
FcRns
are
made
equal.
I
think
during
our
R&D
day
in
the
July,
session
last
year,
we
articulated
key
elements
of
differentiation.
This
is
not
just
a
high
affinity
monoclonal
antibody
targeting
a
target
like
FcRn,
this
is
a
uniquely
designed
ligand
of
FcRn
coming
with
its
own
unique
properties
in
complex
with
FcRn.
I
think
we
demonstrated
some
pretty
fundamental
biological
differentiation,
which
is
again
has
the
potential
to
translate
into
best-in-class
efficacy,
best-in-class
safety
and
convenience. So
as
Keith
said, let's
wait for
safety and
convenience. So
as
Keith
said,
let's
wait
for
the
data.
I
think
we've
put
the
bar
very
high
with
close
to
80%
response
rate
over
the
first
two
treatment
cycles.
And
by
the
way,
response
is
a
very
stringent
definition,
right,
in
four
consecutive
visits
having
a
total
of
two
points
or
more
on
the
ADL
scale.
I
think
if
you
look
at
a
safety
profile,
we
have
shown
unique
interaction
with
FcRn
and
therefore
also
probably
a
very
clean
safety
profile,
which
can
be
unique
and
differentiated.
And
then
on
the
topic
of
convenience,
the
individualized
dosing,
that's
where
we're
going
into
in
this
space.
Also,
the
offering
with
both
IV
and
subcu
I
think
is
giving
maximum
flexibility
to
patients.
So
I
think
we're
well-positioned
to
compete
in
the
FcRn
class.
With
regards to
ITP,
what
to
expect
the
way
we
talk
about
the
first
of
the
two
registration
trials
is
the
primary
endpoint
is
truly
designed
to
create
a
statistically
meaningful
difference
between
active
arm
and
placebo
arm.
There's
not
much
more
to
it
than
that,
but
we
have
gone
to
great
lengths
to
craft
secondary
endpoints,
which
will
give
the
full
opportunity
to
efgartigimod
to
shine
in
an
ITP
indication.
We
will
learn
a
lot
about
cumulative
platelet
counts
in
these
patients,
platelet
counts
over
the
entire
study
period,
the
resulting
bleeding
events,
quality
of
life,
do
not
forget
this
is
a
severe
autoimmune
disease,
it's
much
worse
than
just
a
platelet
count
of
bleeding
issue.
These
patients
suffer
from
debilitating
fatigue,
depression,
anxiety.
And
then,
of
course,
we
want
to
get
some
further
safety
information
on
efgartigimod
in
these
patients.
So
there's
a
lot
of
stuff
to
eat
out
in
this
trial,
but
the
primary
endpoint
is
all
about
hitting
statistically
significant
differentiation
from
placebo.
Operator
And
your
final
question
comes
from
the line
of
Charles
Pitman
from
Redburn.
Your
line
is
open.
C
Charles Pitman
Analyst, Redburn (Europe) Ltd.
Hi,
Charles
Pitman
from
Redburn.
Thank
you very much
for taking
my
questions
sneaking
in
the
end
here.
So
first
is
a
clarifying
question
for
Keith.
Could
you
provide
a
little
– a
little
more
detail
on
your
definition
of
broad
coverage
for
the
US
payers?
And
can
we
assume
this
could
mean
over
50%
of
covered
lives?
And
then
just
secondly,
a
question
for
Karl,
could
you
give
us
just
a
little
bit
more
guidance
on
how
you're
thinking
about
the
COGS
for
VYVGART
and
the
split
between
your
operating
expense
lines
for
2022?
Or
should
we
expect
guidance
to
be
provided
at
1Q
once
the
launch
has
progressed
a
little more?
Thanks.
R
R. Keith Woods
Chief Operating Officer, argenx SE
Yeah,
Charles,
thanks for
the
question.
So
when
we
talk
about
broad
coverage,
remember
we
work
already
with
the
six
national
payers,
and
we
were
before
the
launch,
but
you
also
have
large
regional
papers
that
we're
working
with.
And
so
that's
why
we
said
by
end
of
Q2
because
the
team
is
out
working
with
the
regional
payers
on
the
policies
that
are
being
put
in
place
there.
So
quite
frankly,
giving
the
metric
this
early
of
25%
of
covered
lives,
covered
commercial
lives
at
eight
weeks
in
is
pretty
good.
So
when
I
think
of
broad
coverage,
I'm
not
prepared
to
give
you
a
target,
but
I
do
feel
safe
enough
to
say
I'm
talking
about
greater
than
50%
of
commercial
lives.
T
Tim Van Hauwermeiren
And
thank
you Charles
for
the
question.
In
terms
of
guidance,
we
do
not
plan
to
give
guidance
in
2022.
So
no –
don't
expect
anything
in
Q1.
In
terms
of
COGS,
we're
not
specific
on
the
COGS,
but
you
can
expect
it
to
be
the
same
as
a
typical
biologic.
And
in
terms
of
a
split
on
the
– our
expenses,
again,
we're
not
going
to
give
any
more
detail,
but
I
would
– but
we
– with
the
R&D
will
continue
to
be
the
bulk
of
our
spend
[indiscernible]
(01:04:45).
Thanks,
Charles.
Operator
Ladies
and
gentlemen,
this
concludes
today's
conference
call.
Thank
you
for
your participation,
you
may
now
disconnect.
Good morning. My name is Rob, and I will be your conference operator today. At this time, I would like to welcome everyone to the argenx Fourth Quarter and Full Year 2021 Conference Call.
All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] Thank you.
Beth DelGiacco, Vice President, Investor Relations and Corporate Communications, you may begin your conference.
Thank you, operator. A press release was issued earlier today with our full year 2021 financial results and the recent business update. This can be found on our website along with the presentation for today's webcast.
Before we begin, I'd like to remind you on slide 2 that forward-looking statements may be presented during this call. These may include statements about our future expectations, clinical developments, regulatory timelines, the potential success of our product candidates, financial projections and upcoming milestones. Actual results may differ materially from those indicated by these statements. argenx is not under any obligation to update statements regarding the future or to conform these statements in relation to actual results, unless required by a law.
I'm joined on the call today by Tim Van Hauwermeiren, Chief Executive Officer; Karl Gubitz, Chief Financial Officer; and Keith Woods, Chief Operating Officer.
I'll now turn the call over to Tim.
Good morning and thank you for joining our call today. We had a truly monumental 2021 and ended the year with the FDA approval of VYVGART, a first of its kind FcRn blocker for the treatment of generalized myasthenia gravis in adult patients who are acetylcholine receptor antibody positive. It was a milestone we have been working towards for many years, and we were so gratified to be able to honor our commitment to patients by bringing them a new treatment option. The regulatory momentum continued into 2022 with the subsequent approval of VYVGART in Japan just 34 days later. I cannot emphasize enough the work it took for our teams to make this happen seamlessly. I want to start our call today talking about our launch. During these first weeks, we have focused primarily on demand generation through education and awareness efforts. Keith will share some metrics later in the call, but we still have a lot to learn about our launch trajectory in the coming quarters.
We are doing our best to characterize the state of the launch today, though it's fair to say it's still very early. And these are not necessarily metrics we will share on an ongoing basis, especially as we start to provide revenues during our Q1 earnings call in May. I have had the privilege of being on the road with many members of our field team since the start of the launch. At a high level, we are encouraged by the initial demand in our launch. We know that it is still early days and that we face the same challenges that we described at approval. COVID restrictions, the lack of a J code, the need for physician education and better awareness, but eight weeks into the launch, we are cautiously optimistic and trending well against our plans.
I have also been encouraged by the feedback I'm hearing firsthand from our physicians all of which is consistent with many of the messages we shared leading up to approval. On slide 4, for example, the unmet needs faced by gMG patients for new therapies is significant, and we've seen real demand. The challenge for our salesforce has been demonstrating a sense of urgency during a time when patients do not see their doctors regularly. We also see physicians rethinking how to treat their patients based on the efficacy and safety profile we demonstrated [ph] in adults. (00:04:42) And finally, doctors applaud individualized dosing and the VYVGART label, which allows them the flexibility to dose based on clinical evaluation.
In MG, where every patient is unique and experienced the disease course differently, an individualized approach makes sense to physicians. We believe that the treatment cycle approach will accommodate the majority of our patients. We also want to consider the individual needs of patients that may require alternative or more continuous dosing and to have data should we get questions from providers on this topic. We started a Phase 3b trial called ADAPT NXT to evaluate additional dosing schedules that physicians could use to further individualize the VYVGART treatment approach. As this is a typical Phase 3b trial, we will not be providing additional updates on the study outside of an upcoming medical meeting. In general, we want to have the most complete offering for patients and physicians, whether on a dosing schedule or around formulation, IV or subcu. We continue to believe that having both an IV and subcu option will be important to capture variability in patients and physicians preferences.
Slide 5. Our Phase 3 ADAPT subcu non-inferiority trial is on track to readout this month, evaluating subcu efgartigimod which is co-formulated with Halozyme's validated ENHANZE technology. In this trial, we aim to bridge IV to subcu, based on PD effect, specifically IgG reduction at day 29. We designed our innovative bridging trial, based on a few key points. First, we observed in our clinical trials a linear correlation between IgG reduction and clinical benefit in gMG. We also see a consistent PD effect with efgartigimod whether in healthy volunteers or gMG patients. The disease biology of gMG does not affect PD, and actually, we have seen this in all indications we have studied so far. And finally, in our Phase 1 study of subcu efgartigimod, we observed an identical PD effect with a fixed dose of 1,000 mg subcu, as with 10 milligram per kilogram IV. Beyond the non-inferiority primary endpoint, ADAPT subcu will capture additional safety, efficacy and PK-PD data in the secondary endpoint analysis, which will be important for our commercial team. ADAPT subcu also serves to satisfy our safety database requirements For subcu efgartigimod. We enrolled more than the 50 patients required for the primary endpoint analysis and allowed ADAPT open label extension patients to roll over to the ADAPT subcu trial. We expect to be able to give you an update on timing of our BLA filing when we report top line results. ADAPT subcu is the first of our near term data milestones. We also are on track to share results in the second quarter from the advanced trial, evaluating IV efgartigimod in primary immune thrombocytopenia.
Slide 6. We designed our Phase 3 ADVANCE trial based on the results from our Phase 2 and benchmarking of peer ITP trials. In our Phase 2, we had ambitiously dosed patients for just four weeks while monitoring platelet counts out to 21 weeks. We learned from this trial that more chronic dosing is required in this population, even with the limited drug exposure, we saw responses across patient types in a very refractory ITP population. These results are published in the American Journal of Hematology. We also saw a high placebo response in our Phase 2, which in looking at these trials is very common in ITP given the fluctuating nature of platelets. In our Phase 3, we are dosing patients weekly for 26 weeks with the potential to push the cadence to biweekly dosing based on a stable platelet count. We are measuring the primary end point between weeks 19 and 24, where a patient has to have a stable platelet count, meaning over 50,000 platelets per microliter in at least four of those six visits.
By managing placebo response with this stringent endpoint, we are also setting the efficacy bar high for our treated patients. It will be important to focus on the delta between response in the active and placebo groups. The secondary endpoints will also be important with the advanced readout including safety and tolerability, cumulative platelet counts, bleeding events and quality of life data. This will show a more complete picture of where efgartigimod could play a role in IgG. We hear from physicians that there remains a high unmet need in ITP and that long-term response rates are not satisfactory. Patients typically cycle through treatment options including through multiple TPOs in order to maintain a stable platelet count. Our hope is that we can break this cycle and if an ITP patient fails or relapses on an initial TPO, they will be in a position to try efgartigimod before his second or third TPO. You can see that we have a catalyst rich first half of the year, between our launch progress, and these two data readouts. It's a busy time, but also a very exciting time to finally have our teams in the field engaging with physician customers and serving patients.
I'm going to turn the call to Keith who will provide more details on the VYVGART launch in the US.
Thanks, Tim. Good morning. I'm happy to provide an update on the state of our commercial business. Our salesforce has been in the field for eight weeks now. So we are still in the very early stages. But overall, we are seeing encouraging progress in engaging with our key stakeholders.
Slide 7, please. On our approval call, we talked about our strategic imperatives to empower patients, to provide best-in-class patient support, to ensure rapid adoption from healthcare professionals, and to enable appropriate access. I'm going to share some data from each of these. First, on the patient, we're not going to share patient numbers today, but we are comfortable sharing that we are currently in front of our own projections. We designed our Phase 3 ADAPT study to enroll a broad patient population. Some patients who were on mestinon alone and very early in their disease, while others were much more severe relapsed refractory. With the initial scripts coming in, we see a breadth of patient profiles reflective of the ADAPT population. In the first weeks of launch, we have also seen what we believe is pent-up demand for a new therapy in patients refractory to all other available treatment options. It is too early to know whether or not this is a one-time bolus of patients, but we see these patients contributing to our initial demand.
Slide 8, please. We launched our unbranded DTC campaign in January to create awareness about gMG. The impact of the commercial and empowering patients is clear. The commercial was encouraging patients to learn about new treatment options, including VYVGART. By speaking with their neurologist or downloading resources from the website based on early assessments, approximately 25% of website visits and 50% of phone call inquiries can be tracked back to the DTC campaign.
Slide 9, please. Our patient support program has also been serving our patients and healthcare professionals very well, and approximately 90% of our scripts have come in through My VYVGART Path. We're now seeing scripts translate into infusions, and My VYVGART Path has been crucial to this effort.
Our second strategic imperative is with the physician community. Slide 10, please. Our salesforce has done a great job of engaging with neurologists. The goal was to focus on our top group of targets, which includes about 1,000 neurologists. These neurologists are tiered based on the number of gMG patients that they treat, their likelihood to try a new biologic, and their influence amongst other neurologists. So far, our sales team has reached about 60% of this top target group. Among physicians, we have also seen impressive breadth and depth of prescribers. Groups are not just coming in from our physician champions, but from a broad group, and equally from academic settings as well as the community. We have also seen depth amongst physician prescribers, with many writing scripts for two or more patients. About 60% of our prescribers have been from the top 1,000 neurologist targets.
Our peer-to-peer marketing efforts launched in January, and so far, we have held six national broadcasts and 57 local speaker programs. We have 74 fully trained physician speakers in these first crucial quarters to launch and raise awareness and increase the education on VYVGART.
Finally, our work with payers. Slide 11, please. We announced at approval that we had reached agreements in principle with several national and regional payers to structure a value-based agreement. As of this week, VYVGART's specific policies have been published in plans covering approximately 25% of US commercial lives. We're on track to have broad coverage in place by the end of the second quarter. So far, almost all of the policies are aligned to our label. Patients can gain access if they have previously been treated ineffectively with one or more standard of care options, whether it's mestinon, steroids or a broad immunosuppressant. We are also seeing encouraging prior authorization language approving for 6 to 12 months of treatment at a time rather than based on a specific cycle.
All-in-all, we are optimistic after the first eight weeks of launch, but it is still too early for us to understand how this will play out into future quarters. We look forward to updating you again during our first quarter earnings call.
Before I turn the call over to Karl, I'd like to quickly discuss our global launch strategies. Slide 12, please. The upcoming regulatory milestones are covered in our press release. With Japan, we received approval in January, but the official launch will not start until we have a price. This is typically listed in the months following our approval. Our sales team has been active with neurologists talking about VYVGART and the mechanism of action. They can line up patients before we have a price, but we will not be able to start booking revenues until after the official launch.
In Europe, we expect approval in the second half of the year. And of course, regulatory approval is just the beginning. For the most part outside of Germany, we will not be able to start our promotional efforts until we have secured reimbursement on a country by country basis.
With that, I will turn the call over to Karl.
Thank you, Keith. Slide 13 please. Our 2021 financial results are detailed in your press release from this morning. So I will only highlight some of the key points here. We ended the year with cash, cash equivalents and current financial assets at $32.3 billion. This puts us in a very strong position for our first commercial launch and to execute our plan in 2022. Based on our current plans to fund the business, and assuming successful readouts for each of these programs, we expect to utilize up to half of our all available cash this year.
From a utilization perspective, we think about in the following way. First, R&D and our ongoing clinical trials, we will be in 10 efgartigimod indications by the end of the year and do two ARGX-117 indications. So our development continues to be the largest proportion of our spend. Second, our inventory build and supply chain to support our global launch and global trials, we are building for success to ensure continuity of drug supply to patients. Third, the infrastructure of our global launch, first in the US, then Japan, Europe and Canada. And finally, our continued investment in our discovery engine and the expansion of our pipeline through our immunology innovation program.
For the full year 2021, we had total revenues of $497.3 million. A large majority of this was due to income from collaboration's primarily – primarily but one-time recognition of $315.1 million following the termination of a Janssen collaboration agreement, and our cost sharing and milestone payments from Zai Lab totaling $177.5 million. There were no product revenues in 2021.
Other operating income was $42.1 million. In 2021, our total R&D expenses was $580.5 million, and our SG&A expenses was $307.6 million. As I mentioned at the start, you can find additional details behind these numbers in the press release we issued this morning.
I'll now turn the call back to Tim.
Thanks, Karl. Before I conclude, I'd like to call out a few personal updates. You saw in our press release that Yvonne Greenstreet will be leaving our board following her promotion to CEO at Alnylam. We are very excited for Yvonne and want to express our gratitude for the contributions she made as a board member. We also announced the appointment of Malini Moorthy, the General Counsel at argenx. This was a planned transition and aligns closely with our evolution to a commercial company. Malini has worked in large commercial organizations for almost two decades and has the perfect experience to help us navigate this new stage of our development. And finally, we are nearing April the 1st and our planned CMO transition from Wim Parys to Luc Truyen. Wim has transformed our development organization over the past three years. So we are grateful that he will continue with argenx as an advisor on our board's R&D committee. Luc joined argenx six months ago from J&J and brings significant development experience in the neuromuscular space. We are excited to have him in this leadership role.
Last year was a remarkable year for the company and we're off to a great start in 2022. Slide 14. We have two near-term data readouts, first ADAPT subcu this month and then ADVANCE and ITP in the second quarter. By the end of the first quarter of 2023, we also expect top line data from our CIDP trial and our second trial in ITP. So we're not short of upcoming catalysts. We announced in our press release this morning that the timing of the top line data from the pemphigus trial is currently under review in light of the geopolitical situation in Ukraine. While exposure is limited given the global nature of the trial, we cannot reiterate our timelines until we have time to assess the situation more closely.
The BALLAD trial of efgartigimod and BP started late last year and IQVIA in myositis will start imminently. We also announced four new efgartigimod indications that we will start evaluating this year, including Sjogren's and COVID-19 mediated parts through our collaboration with IQVIA and membranous nephropathy and lupus nephritis through our collaboration with Zai. ARGX-117 is now in our first patient study in MMN, and we are excited to launch a trial in delayed graft function later this year. You can see how our kidney franchise is taking shape. Overall, we are planning for success and building up commercial franchises that will enable us to have economies of scale as we prepare for future launches. And we would not be argenx if we did not continue to invest in our science.
Slide 15. We will be advancing ARGX-119 into a Phase 1 trial after our CTAs filed later this year and through our IAP there are more programs to come. Before we open the call for questions, I really want to applaud our field teams. I have been on the road with them and I'm very impressed. It is thanks to their teamwork and dedication that we have a strong start to our launch, [ph] we shared (00:24:05) the state of our launch in these early days and we look forward to sharing more in May. Mostly, I'm excited to finally be reaching patients and bringing them in new treatment option. This is honoring a commitment we have long made to the gMG community.
Thank you all for the time today. We will now take your questions. [Operator Instructions]
Your first question comes from the line of Derek Archila from Wells Fargo. Your line is open.
Hey, good morning, guys, and congrats on the progress. Just two quick questions from us, I guess, first, based on what you guys are seeing and hearing on the VYVGART launch and myasthenia gravis, I guess are you still pretty comfortable where consensus estimates are right now? And then just a quick follow-up on the ITP study that's expected in the second quarter. Maybe you can just kind of frame out for us what your expectations are there in terms of the primary endpoint and where do you see the market opportunity for efgartigimod in ITP? Thanks.
Hello, Derek. Thank you for your question. In terms of revenue projections, we are not going to comment on the revenue projections at the moment. We don't we're not providing our own forecast. It really is too early in the launch, and we will provide guidance later on. In terms of analysts' consensus, as you know, but the numbers are $97 million for the full year for US revenues and $6 million for the quarter. Those are the analysts' consensus, and we are increasingly comfortable with those numbers.
So on the second question, Derek, and thank you for joining us today. Remember what we learned in the Phase 2 clinical trial, but also what we could see in other ITP trials that is a significant placebo effect going on in ITP patients. So the primary endpoint is a very tough endpoint. It's an endpoint designed to completely control placebo, having in four out of six consecutive visits, a platelets count of kind of 50,000 platelets per microliter is a very tall bar. So the primary endpoint is really designed to create a statistically significant delta between active and placebo. The full color on the qualities of the molecule in ITP and its potential to have a competitive position there will really come from the secondary endpoints where we will study things like cumulative platelet counts, total platelet counts of the period, bleeding effects, quality of life and the like. And that should basically tell us where we could fit in a treatment paradigm. Maybe, Keith, you can comment briefly on how we look at the opportunity.
Yeah. So, Derek, as far as the market opportunity, I guess I would call out the TPO's themselves are doing more than $2 billion in revenue a year globally. And really, where we feel the opportunity is, is we're not going to displace TPO. We would like to play, as Tim said in the prepared remarks, right after the first TPO. So about 60% of patients respond to TPO and about 50% of them are going to then relapse. That's where we feel that efgartigimod can potentially play into it because of its impact on the disease from multiple mechanisms of action. So it's not just about – it's not just about creating more platelets. It's also about managing the clearance, the function of the platelets. So, it should be a better option than patients rotating for one, two or three TPOs.
Got it. Thanks, guys.
Your next question comes from the line of Tazeen Ahmad from Bank of America. Your line is open.
Hi, guys. Good morning. Thanks for taking my question. Just a clarification one for the upcoming subcu dataset that's due this quarter, assuming that the data shows what you wanted to show, can you just walk us through what the next steps would be in terms of going to FDA? And when you think you could file for what I'm assuming would be an FNDA? Just to clarify that. Thank you. Or an FBLA?
Hi Tazeen, this is Tim speaking. Thanks for joining us today and thank you for your question. So, in the United States specifically, the situation with the FDA is that the subcu product, which is in combination with the Halozyme's ENHANZE technology, is considered to be a separate product. So, this is not going to be an FBLA. It will be its own BLA. Therefore, we think it's also its own distinct product presentation we will be able to position in the marketplace. Now, that's great news from a commercial point of view. From a workstream point of view to its submission, we still anticipate that we will be able to reuse big sections of the IVBLA really into that dedicated subcu BLA. Thanks for the question.
Your next question comes from the line of Akash Tewari from Jefferies. Your line is open.
Hey, guys. So, a, the bolus of response that you mentioned, what percent of early scripts have been these ultra-refractory patients and is there any color you can give us on sizing up that market opportunity? Are we talking about a 1,000, 2,000 patients here or something more? And then maybe on the Principia of BTK, which misses primary and secondary endpoint in pemphigus, Sanofi hinted that was due to the high placebo response given the placebo arm also received steroids?
Yeah, I'll take the first question. So, Akash, in regard to what we referenced in the prepared remarks – did we lose?
No.
Okay. Akash, in response to the severe relapse – relapsed refractory that we've seen start in so far in this first eight weeks, I think it was a little bit of a surprise. These are patients that have experienced really all other therapies that are available, including and up to C5 and they have not responded. And so they have come on to VYVGART. So I think that was a little bit of pent-up demand that was a surprise to us. The question is, is this just going to be in the early days because these are the patients that have had no success with any other therapy?
Okay. Sorry. Can you guys hear me?
Yes.
Yeah.
Okay. Sorry about that. So look on the Sanofi, the BTK failing in pemphigus. Can you just comment on in the primary endpoint patients in the placebo arm got tapered down to minimal steroids? They didn't go completely off the drug. Do you feel like that's a risk for your studies, given it looks like steroids in combination with VYVGART was kind of driving some of the complete responses in your Phase 2 data? Thank you.
Thank you, Akash. So difficult for us to comment on, you know, why the Phase 3 trial of Principia failed. Mind you, they failed over the entire line, right? Not just the primary endpoint, but also the secondary endpoints. I think we did our homework well. When we designed our clinical trial, we have been talking to typically those KOLs, who were deeply involved in pemphigus trials, including the Principia trail and rituximab trial. So we think we have been avoiding some of the classical pitfalls in clinical trial design in pemphigus. We are in a steroid taping protocol that is a notoriously difficult protocol, but we're on top of it, so we carefully monitor the steroid tapering. So that goes according to protocol.
Mind you, that the mode of action between the BTK inhibitor and efgartigimod are totally different right, I mean, we're not impacting a B cell repertoire, hoping to see a downstream effect on allergies and disease states. We're really hitting the disease biology in its heart. So we have pretty exciting data from the Phase 2 study that if you eliminate these pathogenic IgGs, you can put patients into a complete remission, actually, a number of them very durable remissions. And stay tuned, I think at the upcoming [ph] SSID (00:32:31) conference later this year, we will continue to show very strong data for our molecule in pemphigus. Thanks for the question.
Your next question comes from the line of Yaron Werber from Cowen. Your line is open.
Great, thanks for taking my question. I got an inter-related question on the upcoming data for ADAPT subcu. We're getting a lot of questions on it. Perhaps the first one, the – you've over enrolled that study. So could you – disclose closed the enrollment with 111 patients or so, you only needed 50 really to support the BLA filing. Are all 111 going to be included in the primary and the secondary endpoints? That's the first question at day 29, and IgG reduction. And then secondly, for the secondary endpoints on MG-ADL, and which you're looking at a 12 weeks, are you going to – do you think you're statistically powered now with 111 patient to show a difference. Thank you.
Thanks, Yaron. I'm happy we can clarify this. So there are two objectives we need to meet right in this study. First is we need to hit the primary endpoint which is all about demonstrating non-inferiority between IV and subcu and in order to do that, we believe that with 50 patients we sufficiently powered. Now the second objective we need to meet is to basically collect the minimum database size which we require for this separate BLA submission. And in that context, you need to see what you called it all recruitment 111 patients. These patients, together with the patients to be rolled over from the open label extension study from IV to subcu together will be a sufficient number of patients and to go into the safety database. So once we have both data points, the primary endpoint and the safety data point, we will be able to go into submission. On the secondary endpoints in the trial, yes, we are collecting information on the ADL and QMG, but this will be more qualitative information because you're right. This study is only powered to hit its primary endpoint. We are collecting, of course, further color and evidence from both the ADL and the QMG score, but it's all about showing a non-inferior IgG reduction. Thank you for the question.
Your next question comes from the line of Joon Lee from Truist Securities. Your line is open.
Hi. Thanks for taking our questions and congrats on all the progress. Is ADDRESS study for pemphigus the only study that's exposed to Eastern European sites including Ukraine or your other studies such as ADVANCE or ADHERE also enroll from Ukrainian sites, but maybe not impacted due to the broader geographic enrollment? And I have a quick follow-up. Thank you.
Thank you, Joon. So all of our trials, by definition, are global trials. So these are all rare indications that all spread over the globe, and that turns out to be a strength. When things hit you like COVID, a COVID pandemic or in this case, a geopolitical issue, so exposure is always going to be relatively limited to whatever study you're talking about.
For pemphigus, we're in a slightly different position because our incidence and prevalence is a little bit tied to geography. I mean, you see different pockets of patients and therefore, we have a slightly higher exposure in Ukraine and Russia and that's also why we felt compelled to give you a heads up on the data readout for pemphigus.
In the ITP subcu and the CIDP study, exposure is minimal, and we have time to rebalance without having to change anything concerning timelines. For pemphigus, we are currently going through the risk analysis, and we will be able to give you an update, probably in the next quarterly earnings call.
Great.
Please, your second question.
Yes, you have a lot of trials underway, which is obviously reflected in your R&D spend. Hopefully, many will succeed, but it's unlikely that all will succeed, similar to what happened with the [indiscernible] (00:36:42) population. So do you have any plans to partner with an AI company to analyze the rich clinical dataset that you're generating and to identify certain biological signatures to improve the odds of your clinical success and we're just asking because we've been talking to a lot of AI companies with autoimmune focus and reducing clinical risks using AI seems to be the focus of many companies and just curious your thoughts on that, since you have a lot of trials ongoing. Thank you.
It's a great question, Joon and whilst we're not deeply engaged within AI, we are following similar strategies. So first of all, these are all rare diseases and there are not too many precedent trials out there or too many data you could mine in an intelligent way. That is a challenge. So we do talk to experts extensively when we design our clinical trials trying to make the studies as diverse as possible when it comes to inclusion exclusion criteria. Also, when it comes to our go/no-go decision points somewhere in these trials where you have the ability, for example, to further tweak certain aspects of the registrational part of the studies. Similar to what we did in CIDP, we're doing that in BP trial. We're doing that in the basket trial in myositis. So I think we find our ways to risk mitigate these studies in an intelligent way. Still I think I'd like to comment, these are still clinical experiments, which all have their own intrinsic risks associated. Thanks for the question.
Your next question comes from the line of Yatin Suneja from Guggenheim Partners. Your line is open.
Hey, guys, thank you for taking my question. So question is on the patient population, so when you talk about the 17,000 the gMG patients that you are targeting, can you maybe help us subcategories these patients. It is our understanding that there are different categories within these 17,000, and some might be more or might be easier patient to get early in the launch curve, like patients who are on chronic IVIg, maybe Soliris non-responder. So if you can just give us a flavor of what exactly you are seeing in these buckets, how big are these buckets, and how should we expect some of these buckets that are maybe first to come to your therapy. So that's the first question. And the second one and last right now is on the J code, can you also talk about what a limitation it might be having, if any, at this point and how that dynamic would change once you once you get it in Q3, so two questions for me. Thanks.
Great. Well, thank you for the question, Yatin. First of all, what I'd say is the patient population that we are seeing that is adapting VYVGART in this early period, this first eight weeks is really aligned with the ADAPT trial. It is really across the treatment spectrum. As I mentioned, we are getting some relapsed refractory patients. We've also had some from IVIg. But typically when you look at that target population of 17,000, these are patients that have tried [ph] myasthenia (00:39:56) many times they've had a steroid added and many of them have also gone on an off label broad IST. And we have seen each of those types of patients experience VYVGART in the early stages of the launch. As far as your second question on the J code and the limitations, what the J code basically does, it's in the buy-and-bill situation and it is putting more work on the office to get reimbursed. It's not that it makes it where it cannot be reimbursed because we are having product reimbursed in buy-and-bill setting. It just may add an extra step of going through an appeal process, and it puts more work on the office staff. You also have a limited number of offices that actually elect not to prescribe a product, why they don't have a J code because they don't want to put the extra work on the office. I think the last thing that we need to remember is unlike an oncology setting, your buy-and-bill market in neurology is smaller than what you see in [indiscernible] (00:40:56) and it's really in that buy-and-bill where you see the J code impact. But we expect to have our own individualized J code in quarter three.
Your next question comes from the line of James Gordon from JPMorgan. Your line is open.
Hello, James Gordon, JPMorgan. Thanks for taking the questions. The first question was just, so with regard to MG. How important do you think first mover status is and formulation relative to other FcRns in MG? And I also want to ask whether UCB are going to present their roza FcRn Phase 3 data at ALL next month. And they talked very confidently about how they're going to present data that shows it's very competitive versus VYVGART. So, do you think there are areas where they could actually be competitive or given the first mover advantage formulation of other aspects, et cetera? Other areas where there could be a risk factor? How are you feeling about that ? The first question.
I'll ask a follow-up now, which was just on Russia-Ukraine disruption, and I think the comment on PV and potential delays there. But the ITP subcu trial looks like it's got quite a lot of rush inside. And I think about a third of the sites that are out there in Russia. So is there a risk that that study is also going to be disrupted and delayed? Or is it more of an issue if it's Ukraine versus Russia?
Yeah. Let me start with the second question first, and I'm happy to hand over to Keith to talk about our competitive position in the MG landscape. It's still just about the sites which you can see on clinicaltrials.gov, but it's about the actual number of patients which actually have been enrolled through this sites. So, when we look at the real situation, which is actual number of patients, we feel that the subcu study for efgartigimod in ITP is perfectly under control, I would say that indeed there is somewhat more exposure in the pemphigus trial. So, maybe we will have to overcompensate that in some of the sites that is analysis which is ongoing. And so, I don't think there's any reason to change the guidance on readouts timing for the ITP subcu custody or the CIDP subcu custody. Maybe Keith you want to comment on how we look at our competitive position in the MG landscape.
Sure. So James, first of all, I think it's premature to comment anything on the Phase 3 data because we haven't seen any specific data at all. As far as the first mover advantage, I think that the opportunity that exists with VYVGART is based on the data itself. Let start with the efficacy. Between the first and second cycle almost 8 out of every 10 patients that experienced VYVGART are going to have a clinically meaningful response. We also have a very rapid onset of action with 84% of them responding within the first two weeks and the minimal symptom expression, sending these patients to where they have no symptoms at all. Right now, it's the highest number that's been recorded in a clinical trial. Secondly, take a look at the package insert that we have. It is very clean. The safety profile, this is one of the things that we're hearing from the physicians that are prescribing. They're impressed about this. There's no premeditation. There's no black box warning and the safety is riding up through all of our studies. The last thing I would say is individualized dosing. We are providing convenience to patients when they can take advantage of the individualized dosing. And so I guess what I would say is we've set the bar high, but let's wait and see data.
Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is open.
Great. Good morning. Thanks for taking the questions. I guess two for me. One, I don't know if you're willing, but it would be interesting to hear what you're sort of seeing on a month over month basis? Are you seeing patients accelerate or not? Just so we can get some sense of how you're thinking about the bolus. And then second question, just because I think a lot of us haven't seen a Japan launch before. Can you give us some sense of whether or not you think Japan can be a meaningful contributor this year? And just given the commentary around when you get the price, but the fact that it sounds like you can already start to line up patients? Thanks very much.
Yeah. Hey, Matthew. Thanks, thanks very much for the question. So as far as what we're seeing on a month over month basis, we've only had eight weeks. So it's really tough to give you a month over month basis. I can tell you that we're – what we're seeing in patient demand, it's been gradual, and it's been consistent. I think that we have prepared well in ADVANCE on each of those strategic imperatives. And I think the team is out there executing on each of the areas, whether it's the patient awareness, the healthcare professionals or the payers. I'm also really pleased with the progress that we have through My VYVGART Path, because when you have a brand new first in class product with a brand new mechanism of action, there does take some pull through to turn demand into actual infused patients.
So we can talk a little bit more about patient trends when we actually get to a first quarter earnings call. As far as your second question about the Japan launch, again, I'm going to advise on a very gradual, consistent growth because we run into the same issue that exists in the United States and that is education on a first ever mechanism of action. And also, I would call out to you that the number of clinical trial sites that we had in Japan is smaller than what we even experienced in the US. So I wouldn't think of you have a bolus of patients that are set to go. Now one thing that we do have different in Japan, I remind you that in the approval that we received in January, the Japan label will include zero negative patients.
Your next question comes from the line of Allison Bratzel from Piper Sandler. Your line is open.
Hi, good morning. Thank you for taking the question. So just one on the source of the [ph] patients, (00:46:57) having sat through some of the gMG patient webinars about VYVGART. It seems like there's definite interest not just in switching from IVIg, but surprisingly in switching from Soliris as well, so I know it's early days, but does that match, what you're seeing in the field? And then I guess just to the extent that you are seeing patients having an interest in switching from Soliris to VYVGART, what's the primary driver or reason behind that from a patient and neurologist point of view and just how do you expect that dynamic to evolve when Ultomiris gets a gMG label mid-year? Thanks.
Yeah. So thank you for the question, Allison. I guess the first thing that I would say is it's too early to predict a trend, because we're talking about individual patients. And as you know, in rare disease, every single patient is different. And we also know just from the data that you're not going to get every single patient to respond to a therapy. You can go back and look at the REGAIN study or the data that was released on Ultomiris. So regardless of what product the patient has gone on, you're going to have a part of that population that is not going to respond. And when they have not responded, they're going to look for other options. And that's what's happened with VYVGART becoming another tool to place in the box of the healthcare professionals.
Your next question comes from the line of Douglas Tsao from H.C. Wainwright. Your line is open.
Hi, good morning and thanks for taking the questions. I'm just curious on the ADAPT NXT trial, did you start that sort of based on any sort of questions from providers to provide clarity in terms of the sort of dosing regimens and have you gotten an early sense about how physicians are going to implement the individualized dosing that you have in the label? Thank you.
Yeah. So Douglas, we have been working with a group of KOLs for better than two years now. It's been since the Phase 2 data that we discuss the concept of individualized dosing. It first came from the patients when we shared with them the Phase 2 data, and they love the idea of the cycles, and they love the idea of having the time off therapy. We then went and discussed this with the KOLs, and they've seen the data and they're very pleased with it. The question that they had is what if I require somebody that might need a little bit more consistent dosing? And what we always aim to do is to be able to have data based answers, and that's basically what this trial has been set up for.
I think the other way to look at this is, look, we have a long term commitment to the MG space and what we want to offer MG patients around the globe is the most complete offering and the way you have to understand the most complete offering is maximum flexibility from a dosing point of view. This is a snowflake disease. Every MG patient is different. You cannot basically take them to the same standard approach. And we also want to have flexibility from a product presentation point of view. There are different preferences and needs out there in the market for both an IV product and a subcu products. So look at it through this lens.
Okay. Great. And again, one follow-up. Just in the early days, have you had any sort of color on how docs are implementing with the individualized dosing?
Yeah. So I mean, first of all, they like the idea of the individualized dosing. They like the idea of only treating a patient when they need therapy. They also like the idea of the data that they've seen in what percentage of patients. As you know, during the launch, we shared with you that 58% of patients require five cycles or fewer. The questions that they've had is how should they start the patient and how do I figure out, how to get the individualized dose that my patient needs? And a lot of them have taken a look at how they utilizes off-label IVIG to treat MG, and that is basically let's get our patient into response and get that patient to the maximum response that we can have. And then as we have the patient in response based on the label, it's their clinical evaluation and their discussion with the patient on how they stretch that interval out. And that's what we've seen happen in the open label extension, and that's what we'll see happen in the real world.
Your next question comes from the line of Danielle Brill from Raymond James. Your line is open.
Hi, guys, good morning. Congrats on the progress and thanks so much for the questions. I have a couple on ITP. Can you mention placebo responses are common, but I believe the placebo response rate was actually pretty low in [ph] Rigel's (00:51:53) program, are there specific differences in the population [ph] they enrolled versus (00:51:57) those in ADVANCE that might explain this? And then in their Phase 3 publication they showed efficacy was much lower in patients who are antibody negative. I'm just wondering how we should think about potential risk of including antibody negative patients in ADVANCE. Thank you.
Thank you, Danielle. [Technical Difficulty] (00:52:15) some questions. So first of all, the reason the placebo response was low in the [ph] Rachel (00:52:19) trial is because they basically have used a similar endpoint as the one we're using. So we have been studying that trial in detail. They also had an adjustable platelet response requirement. So unlike the PPO registration trials where after a certain period of treatment, it was sufficient to be at 50,000 platelets are higher on a specific day. They built in the durability requirement, and you can indeed see how effective that has been in knocking down the placebo. I think in one trial they had 0% response. And then in another trial, they had something like a 1% response in placebo and basically was trying to achieve similar numbers on placebo by applying similarly stringent endpoint.
Now this story on antibody negative patients, I don't think that exists. I mean all ITP patients. Primary ITP patients do have autoantibodies styling the platelets. The issue is what test you use to analyze the antibody levels and what the sensitivity is, what the detection limit is for these patients. So for example, in our Phase 2 trial, we use a more sophisticated method where we basically harvest platelets, we strip the autoantibodies from the platelets and then we semi quantify them, 100% of the patients actually is autoantibody positive. So if you have a true primary ITP patient, that patient will have platelet associated autoantibodies. Thank you for the questions.
Your next question comes from the line of Jason Butler from JMP Securities. Your line is open.
Hi, thanks for taking the question. Just one from me on reimbursement, I'm just looking forward to the subcu products, given that that products in VYVGART will be distinct. Will the value based agreements in place for VYVGART expand immediately on approval for the subcu subgroup product? Or do you need to go through another process because they're distinct products? And then same question essentially for the J code part of the equation, will you need to get a separate J code for the subcu products? And while you wait for it, will the J code you have in place for VYVGART help in any way? Thanks.
Yeah, Jason, thank you for the questions. So, first of all, you know, the work that we did with payers in ADVANCE by putting them under CDA prior to even having approval of VYVGART. And that's when we discussed all of the data with them, including what we saw on the distribution on the number of cycles per year, we looked at the patient population. We know that the IV was weight based dose. And so we really discussed them what would make sense in regard to a value-based agreement with them. We have not yet made the decision on exactly how we will handle as we have the approval for subcu but in a true collaboration goal that we've had with our IV launch, we will be out with these same payers in ADVANCE of a subcu approval to determine what will be the best method to take considering it will be a separately branded product. Secondly, you asked the question about the J code. I think that once you have a subcu product that would be available for patients to give themself a simple single injection at home, you're going to see by far the majority of that subcu product acquired through specialty pharmacy. And so that's not going to come into play with the J code to the same level that you're seeing with a buy and bill infusion IV product.
Your next question comes from the line of Joel Beatty from Baird. Your line is open.
Hi. Thanks for taking the questions. First one is, can you describe how the patient experience has been from the time of prescription of VYVGART to actually starting on therapy such as what percent of prescriptions are being filled right now and how long it takes to start on drug ? Then the second question is what is the status of VYVGART being added to treatment guidelines for gMG?
Yeah, so first, let's talk about the experience from the time that the script was wrote to the time that the patient is infused and the reality of it is you have a brand new product that's out and available. And what we're – what we're seeing is on a patient by patient basis. It completely depends upon who their insurer is. What we do know as we don't have a J code, as you've heard in the prepared remarks, the policies that are being prepared by the payers, we have about 25% of covered lives that have policies in place right now. So the process going from demand to actual infusions in some cases is longer. We expect this to shorten over time. But I'm really proud of the team at my VYVGART our nurse case managers, our case coordinators and our field reimbursement managers who are working on every single case to make sure that we can shorten the time to the best of our ability. So what was the second question, please?
VYVGART being incorporated into treatment guidelines for general.
We're eight weeks into this initial launch and really, it's too early to say. Right now, the only thing I can say is the treatment guidelines of where we are seeing patients that are being prescribed. VYVGART is aligned with ADAPT, so it's not necessarily severe relapsed refractory. In some cases, it's much earlier in the treatment paradigm. But I'm sure we will see more treatment guidelines over time as the market matures.
Your next question comes from the line of Manos Mastorakis from Deutsche Bank. Your line is open.
Yes, hello. Thank you for the question. So, yeah, you alluded to that already very briefly. But I just want to better understand your latest perspective on clinical differentiation to competitors such as [indiscernible] (00:58:26) may be coming in the future, as well as competitive risk from broader use C5 inhibitors in MG if Ultomiris is approved. And a follow-up question, Is what would your expectations be for the Phase 3 ITP data and the clinical positioning as well in ITP?
The elements we mentioned. So let's start with the biology, right. I mean, we're a science based. We follow biology. Myasthenia Gravis is truly an IgG mediated disease. So the pathogenic IgG antibodies are very well-known. We also know what they do at the neuromuscular junction by binding acetylcholine receptors or other building blocks of the junction. They will basically prevent signaling through the acetylcholine receptors. They will basically crosslink, internalize and make the receptor unavailable for signaling, and they will also recruit components. So definitely complement this one of the several pathogenic modes of action of these autoantibodies. And by nature of the disease biology, if you clear the autoantibody, you will of course, eliminate complement recruitment to the junction. But you will also effectively take care of the older pathogenic modes of action of these autoantibodies. So with upstream of any complement blocker. And I think we have a more complete blockade of the disease biology in the pinnacle of data support that has got taken what has shown the highest ever clinical efficacy in any clinical trial. What about the differentiation within the FcRn class? I think it's extremely important. You guys remember that not all FcRns are made equal.
I think during our R&D day in the July, session last year, we articulated key elements of differentiation. This is not just a high affinity monoclonal antibody targeting a target like FcRn, this is a uniquely designed ligand of FcRn coming with its own unique properties in complex with FcRn. I think we demonstrated some pretty fundamental biological differentiation, which is again has the potential to translate into best-in-class efficacy, best-in-class safety and convenience. So as Keith said, let's wait for safety and convenience. So as Keith said, let's wait for the data. I think we've put the bar very high with close to 80% response rate over the first two treatment cycles. And by the way, response is a very stringent definition, right, in four consecutive visits having a total of two points or more on the ADL scale. I think if you look at a safety profile, we have shown unique interaction with FcRn and therefore also probably a very clean safety profile, which can be unique and differentiated.
And then on the topic of convenience, the individualized dosing, that's where we're going into in this space. Also, the offering with both IV and subcu I think is giving maximum flexibility to patients. So I think we're well-positioned to compete in the FcRn class. With regards to ITP, what to expect the way we talk about the first of the two registration trials is the primary endpoint is truly designed to create a statistically meaningful difference between active arm and placebo arm. There's not much more to it than that, but we have gone to great lengths to craft secondary endpoints, which will give the full opportunity to efgartigimod to shine in an ITP indication. We will learn a lot about cumulative platelet counts in these patients, platelet counts over the entire study period, the resulting bleeding events, quality of life, do not forget this is a severe autoimmune disease, it's much worse than just a platelet count of bleeding issue. These patients suffer from debilitating fatigue, depression, anxiety. And then, of course, we want to get some further safety information on efgartigimod in these patients. So there's a lot of stuff to eat out in this trial, but the primary endpoint is all about hitting statistically significant differentiation from placebo.
And your final question comes from the line of Charles Pitman from Redburn. Your line is open.
Hi, Charles Pitman from Redburn. Thank you very much for taking my questions sneaking in the end here. So first is a clarifying question for Keith. Could you provide a little – a little more detail on your definition of broad coverage for the US payers? And can we assume this could mean over 50% of covered lives? And then just secondly, a question for Karl, could you give us just a little bit more guidance on how you're thinking about the COGS for VYVGART and the split between your operating expense lines for 2022? Or should we expect guidance to be provided at 1Q once the launch has progressed a little more? Thanks.
Yeah, Charles, thanks for the question. So when we talk about broad coverage, remember we work already with the six national payers, and we were before the launch, but you also have large regional papers that we're working with. And so that's why we said by end of Q2 because the team is out working with the regional payers on the policies that are being put in place there. So quite frankly, giving the metric this early of 25% of covered lives, covered commercial lives at eight weeks in is pretty good. So when I think of broad coverage, I'm not prepared to give you a target, but I do feel safe enough to say I'm talking about greater than 50% of commercial lives.
And thank you Charles for the question. In terms of guidance, we do not plan to give guidance in 2022. So no – don't expect anything in Q1. In terms of COGS, we're not specific on the COGS, but you can expect it to be the same as a typical biologic. And in terms of a split on the – our expenses, again, we're not going to give any more detail, but I would – but we – with the R&D will continue to be the bulk of our spend [indiscernible] (01:04:45). Thanks, Charles.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, you may now disconnect.