EX-99.2 3 d754931dex992.htm EX-99.2 EX-99.2
A Phase 1, Open-Label, Multicenter Study to Assess the Safety,
Tolerability, and Immunogenicity of mRNA-4157 Alone in
Subjects With Resected Solid Tumors and in Combination With
Pembrolizumab in Subjects With Unresectable Solid Tumors
(Keynote-603)
Saturday 01 June 2019
Copyright © 2019 Moderna
Slide
1
Exhibit 99.2


Background
Copyright © 2019 Moderna
T-cell
targeting
of
mutation-derived
epitopes
(neoantigens)
has
been
demonstrated
to
drive
anti-tumor
responses
Immunizing
patients
against
such
neoantigens
in
combination
with
a
checkpoint
inhibitor
(CPI)
may
elicit
greater
anti-tumor
responses
than
CPI
alone
Mutations
are
rarely
shared
between
patients,
thus
requiring
a
personalized
approach
to
vaccine
design


mRNA-4157
is
a
personalized
neoantigen
cancer
vaccine
encoding
up
to
20
neoantigens:
(going
forward
all
patients
will
receive
a
vaccine
encoding
up
to
34
neoantigens)
Individually
designed
and
manufactured
for
each
patient
Encapsulated
in
a
proprietary
lipid
nanoparticle
and
delivered
intramuscularly
Selected
using
a
proprietary
algorithm
based
upon
each
patient’s
HLA
type
and
tumor
mutanome
from
whole
exome
DNA
and
RNA
sequencing
from
tumor
and
blood
samples
Personalized cancer vaccine process
Copyright © 2019 Moderna


Study design
Copyright © 2019 Moderna
0.04 mg
n=3
0.13 mg
n=6
1.0 mg
n=1
0.39 mg
n=3
0.04 mg
n=5
0.13 mg
n=5
1.0 mg
n=5
0.39 mg
n=8
Part A (Adjuvant patients):
Monotherapy mRNA-4157
Part B (Metastatic patients):
mRNA-4157 + pembrolizumab
Dose escalation cohorts
Histologies
in
part
A
and
B:
NSCLC
SCLC
Cutaneous
melanoma
HPV
negative
HNSCC
Bladder
urothelial
carcinoma
MSI
high
malignancies
TMB
high
malignancies
Objectives:
Safety
and
tolerability
of
mRNA-4157
monotherapy
and
in
combination
with
pembrolizumab
Biomarkers
including
antigen
T-cell
responses
Anti-tumor
activity


Study design
Copyright © 2019 Moderna
Screening
period
pembrolizumab
monotherapy
run-in* (Dosing
every 21 days
for 2 cycles)
mRNA-4157
+pembrolizumab
(Dosing every 21
days for up to 9
cycles)
pembrolizumab
monotherapy
(Dosing up to
35 cycles)
Safety
follow-up
(100 day
post
treatment)
*Part A patients are adjuvant patients receiving mRNA-4157 monotherapy.
Pembrolizumab run-in and pembrolizumab monotherapy period does not apply


Patient demographics
Copyright © 2019 Moderna
Part
A:
13
Part B: 23
Age(y)
Range:
52-85
45-88
Median:
67
64
Sex
Male:
6
13
Female:
7
10
Race:
Caucasian
13
19
Black
-
1
Asian
-
1
Histologies
N =36
Part A
13
Melanoma
3
MSI
HIGH/MMR
Deficient
Colorectal Carcinoma
2
Non-small
Cell
Lung
Cancer
8
Part B
23
TMB High
Metastatic squamous cell cancer of the skin
1
Bladder
Urothelial
Carcinoma
5
HNSCC
2
Melanoma
1
MSI
HIGH/MMR
Deficient
Colorectal Carcinoma
2
Metastatic Castrate Resistant Prostate Carcinoma
1
Endometrial Carcinoma
1
Non-small
Cell
Lung
Cancer
8
Small
Cell
Lung
Cancer
2
Part B Prior Therapies
N=23 (%)
Number
of
patients
received
at
least
1
prior
therapy
22 (95.6)
Number of patient received
prior checkpoint inhibitors
Number
of
Prior Therapies
15 (65.2)
0
1
(
4.3)
1
3
(
13.0)
2
6
(26.1)
3
2
(8.7)
3+
11
(47.8)


Safety data
Copyright © 2019 Moderna
Related
AEs of at least grade 2 highest grade reported once per patient
Related Adverse Event*
Grade 2
Grade 3
Part A: mRNA-4157 monotherapy
4
0
LEFT ARM PAIN
1
-
COLITIS
1
-
FATIGUE
1
-
MYALGIAS
1
-
Part B: pembrolizumab monotherapy
3
4
DIARRHEA
-
1
AMYLASE INCREASE
-
1
LIPASE INCREASE
-
1
ELEVATED AST
1
-
ANEMIA
1
-
WORSENED DYSPNEA
1
-
ELEVATED GGT
-
1
Part B: mRNA-4157 & pembrolizumab
0
0
No mRNA-4157 related grade 3/4 AEs were reported


Part A: Adjuvant patients receiving mRNA-4157
monotherapy
Copyright © 2019 Moderna
13
adjuvant
patients
have
been
treated
with
mRNA-4157
13
patients
have
completed
full
course
of
vaccination
per
protocol
11
patients
remain
disease
free
up
to
72
weeks
on
study


Part B: Metastatic patients receiving mRNA-
4157/pembrolizumab combination
Copyright © 2019 Moderna
20
out
of
23
advanced/metastatic
patients
have
been
treated
with
mRNA-4157/pembrolizumab
combination
1
patient
with
MSI-High
CRC
had
a
CR
on
pembrolizumab
monotherapy
prior
to
vaccination
5
patients
had
a
PR
including
2
patients
who
have
progressed
with
prior
checkpoint
inhibitor
therapy
7
patients
had
stable
disease
and
10
patients
remain
on
study
treatment
with
ongoing
clinical
benefit
as
of
10-May-2019


Best overall response
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Patient 40019 –
Small cell lung carcinoma
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Patient 40031 –
Small cell lung carcinoma
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Patient 40023 –
Bladder carcinoma
Baseline
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Copyright © 2019 Moderna
Patient
was
dosed
with
1mg
of
vaccine
monotherapy
and
underwent
apheresis
at
baseline
and
7d
post
4th
dose.
Increases
in
ex
vivo
(unexpanded)
T-cell
responses
were
detected
against
all
neoantigen
pulsed
DC
pools
post
vaccination
(A).
Increases
in
in
vitro
stimulated
(IVS,
expanded)
T-cell
responses
were
detected
against
all
neoantigen
pulsed
DCs
pools
post
vaccination
(B).
All
positive
CD8
T-cell
responses
post
vaccination
were
to
neoantigens
with
high
predicted
binding
affinity
of
<
500
nm.
Patient 40033 neoantigen specific CD8 T cell response data
A
B


Robust CD8 T cell responses detected post-vaccine dose 4 to
55% of predicted class I neoantigens
Copyright © 2019 Moderna
CD8 T cell responses to individual
neoantigens were measured in in vitro
stimulated (IVS, expanded) T cells
Flow cytometry plots show increases in %
freq.
of
CD8
cells
producing
IFN 
7d
post
4
th
vaccine dose to multiple neoantigens
Greater than 3x (*in summary graph)
increases in neoantigen specific CD8 T-cells
were detected post vaccination against 10
out of 18 class I targeted neoantigens
included in patient 40033 vaccine


Conclusions
Copyright © 2019 Moderna
mRNA-4157
is
well
tolerated
at
all
dose
levels
studied
with
no
DLTs
reported
No
mRNA-4157
related
grade
3/4
AE
or
SAE
was
reported
Clinical
responses
have
been
seen
in
6
out
of
20
patients
treated
with
mRNA-4157/pembrolizumab
combination.
Of
these
6
patients
with
responses,
2
were
observed
in
patients
previously
treated
with
a
PD-(L)1
inhibitor.
Neoantigen
specific
CD8
T-cell
responses
were
detected
to
10
out
of
18
class
I
neoantigens
included
in
patient
40033
vaccine,
the
first
patient
dosed
at
1
mg
who
underwent
apheresis.
100%
of
positive
CD8
T-cell
responses
post
vaccination
were
to
neoantigens
with
a
high
predicted
binding
affinity
of
<
500
nm
Safety,
tolerability
and
immunogenicity
data
supports
the
advancement
of
mRNA-4157
to
phase
II
at
the
1
mg
dose


We’d like to thank all of the patients, their families, and care givers for
their participation in this trial.
Thank You!
Copyright © 2019 Moderna