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Merck ASCO 2014 Investor Briefing

This presentation includes “forward-looking statements” within the meaning of the safe harbor
provisions of the United States Private Securities Litigation Reform Act of 1995. These statements
are based upon the current beliefs and expectations of Merck’s management and are subject to
significant risks and uncertainties. There can be no guarantees with respect to pipeline products that
the products will receive the necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties
materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general industry conditions and competition;
general economic factors, including interest rate and currency exchange rate fluctuations; the impact
of pharmaceutical industry regulation and health care legislation in the United States and
internationally; global trends toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent in new product development,
including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of international economies and sovereign risk;
dependence on the effectiveness of Merck’s patents and other protections for innovative products;
and the exposure to litigation, including patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can be found in Merck’s 2013
Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange
Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Forward-Looking Statement
Agenda
• Opening Comments: Dr. Roger Perlmutter

• Melanoma and NSCLC Review: Dr. Roy Baynes

• Head & Neck Review: Dr. Tanguy Seiwert (University of Chicago)

• Harnessing Mechanisms in Immuno-Oncology: Dr. Roy Baynes

• Q&A
Merck ASCO 2014 Investor Briefing
• Pembrolizumab (MK-3475) has potential to be 1
st
Anti-PD-1
• Robust anti-tumor activity across 3 tumor types in multiple lines
• 16 presentations/posters at ASCO, including 6 oral presentations
– Advanced melanoma
– Non-small-cell lung cancer
– Head & neck cancer
• Studies ongoing in 30 tumor types as monotherapy and combination
Merck’s Strategy in Immuno-Oncology
• Building a foundation with monotherapy
– Beginning with refractory patients
– Expanding into earlier stages
– Exploring multiple tumor types
– Providing broadest clinical data set
• Expanding experience in combination therapy
– Standard of care, emerging approaches, and other immunotherapy agents
Advanced Melanoma Highlights
Roy D. Baynes
Senior Vice President
Global Clinical Development
Merck Research Laboratories
Prior IPI and Dose
Abstract 3000:
O. Hamid, Tues, June 3
9:45 am in S100a
411 Patients in Melanoma Expansion Cohorts:
KEYNOTE-001
11 2012 2013
D J F M A M J J A S O N D J F M A M A S O
IPI Naïve
10 mg/kg Q2W
(n = 41)
IPI Naïve
10 mg/kg Q3W
(n = 24)
IPI Naïve
2 mg/kg Q3W
(n = 22)
IPI Treated
10 mg/kg Q2W
(n = 16)
IPI Treated
10 mg/kg Q3W
(n = 32)
IPI Refractory
10 vs 2 mg/kg Q3W
(n = 173)
IPI Naïve
10 vs 2 mg/kg Q3W
(n = 103)
Cutoff for current analysis
(18 October 2013)
Presented by: Antoni Ribas
Role of PD-L1
Abstract 3005:
R. Kefford, Tues, June 3
11:09 am in S100a
irRC vs RECIST
Abstract 3006:
F.S. Hodi, Tues, June 3
11:21 am in S100a
Nonrandomized cohorts
(N = 135)
Randomized cohorts
(N = 276)
Maximum Percent Change from Baseline in
Tumor Size
a
(Central Review, RECIST v1.1)
Presented by: Antoni Ribas
a
In patients with measurable disease at baseline by RECIST v1.1 by central review and ≥1 postbaseline assessment (n = 317).
Percentage changes >100% were truncated at 100%.
Analysis cut-off date: October 18, 2013.
Individual Patients Treated With Pembrolizumab
-100
-80
-60
-40
-20
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20
40
60
80
100
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%

IPI-T
IPI-N
72%
Antitumor Activity by Prior Ipilimumab and
Pembrolizumab Dose/Schedule
• Prospective randomized testing of
2 mg/kg Q3W vs 10 mg/kg Q3W
(N = 276; Hamid et al, Abstract 3000)
and 10 mg/kg Q3W vs 10 mg/kg Q2W
(N = 244; not reported) does not
suggest superiority of any one dose
regimen
Presented by: Antoni Ribas

a
Assessed by independent central review in patients with measurable disease
by RECIST v1.1 by central review at baseline.

b
Assessed by investigator review.
Analysis cut-off date: October 18, 2013.
N CR, %
ORR, %
(95% CI)
RECIST v1.1
a
IPI-N 168 8 40 (32-48)
IPI-T 197 2 28 (22-35)
Total 365 5 34 (29-39)
irRC
b
IPI-N 190 8 43 (36-51)
IPI-T 221 3 31 (25-37)
Total 411 5 37 (32-41)

Presented by:
Time to and Durability of Response (Central Review, RECIST v1.1)
Presented by: Antoni Ribas
a
Ongoing response defined as alive, progression free, and without new anticancer therapy.
Analysis cut-off date: October 18, 2013.
IPI-T
IPI-N
Complete Response
Partial Response
Progression
On Treatment
Time, weeks
10 30 50 70 90
I
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12 months 6 months 18 months
• 88% of responses ongoing
a

• Median response duration
not reached (range, 6+ to
76+ weeks)
Kaplan-Meier Estimate of Overall Survival
Presented by: Antoni Ribas
a
OS rate at 18 months is driven by the 135 patients enrolled in the nonrandomized cohorts because they have the longest follow-up duration.

Analysis cut-off date: May 2014.
• Median OS not reached
• 69% OS rate at 12 months (74% for IPI-N, 65% for IPI-T)
• 62% OS rate at 18 months
a

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%

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
0
10
20
30
40
50
60
70
80
90
100
Time, months
411 388 347 324 307 281 250 208 156 95 78 62 27 6 0
n at risk
Treatment-Related AEs With Incidence >5%
• No treatment-related deaths
• Similar safety profiles in IPI-N and IPI-T patients
Presented by: Antoni Ribas
Adverse Event, %
Total
N = 411
Any Grade Grade 3/4
Fatigue 36 2
Pruritus 24 <1
Rash 20 <1
Diarrhea 16 <1
Arthralgia 16 0
Nausea 12 <1
Vitiligo 11 0
Asthenia 9 0
Cough 9 0
Adverse Event, n (%)
Total
N = 411
Any Grade Grade 3/4
Myalgia 9 0
Headache 8 <1
Hypothyroidism 8 <1
Decreased appetite 7 <1
Dyspnea 7 <1
Chills 6 0
Pyrexia 6 0
ALT increased 5 <1
Total 83 12
Analysis cut-off date: October 18, 2013.
Summary
• Overall, 34% ORR (RECIST v1.1, central review)
– 40% ORR in IPI-N patients
– 44% ORR in treatment-naïve patients
– 28% ORR in IPI-T patients
• Responses are durable for both IPI-N and IPI-T
– 88% of responses ongoing
– Median duration of response not reached (range, 6+ to 76+ weeks)
• Median PFS of 5.5 months
• 69% OS rate at 1 year (median OS not reached)
• Manageable safety profile across doses in IPI-N and IPI-T patients
• Pembrolizumab, across all dose regimens tested, provided a favorable
benefit-risk profile, suggesting it is a promising treatment option for
patients with advanced melanoma
Presented by: Antoni Ribas
NSCLC Highlights
Roy D. Baynes
Senior Vice President
Global Clinical Development
Merck Research Laboratories
KEYNOTE-001: PD-L1 Expression in
Previously Untreated NSCLC
Previously Untreated Patients With
Advanced NSCLC Screened for PD-L1
N = 84
Presented by: Naiyer A. Rizvi
62%
PD-L1
+
in 2L+
Tumor Biopsy Evaluable for PD-L1
n = 73
PD-L1
+
Tumors (Proportion Score ≥1)
n = 57
78%
PD-L1
+

Patients Eligible for Treatment with
Evaluable Imaging at Baseline by irRC
n = 45

Patients with Evaluable Imaging at
Baseline by RECIST v1.1
n = 42


Analysis cut-off date: March 3, 2014.
Total (N = 45) On Therapy (n = 25)
Time on therapy, days,
mean (range)
154 (1-400) 218 (126-400)
Number of doses, median
(range)
9 (1-23) 11 (7-23)
Discontinued Patient/
Physician Choice
n = 5 (11%)
KEYNOTE-001: Patient Disposition
Patients With Initial Treatment from
March 4, 2013 to November 7, 2013
N = 45
Presented by: Naiyer A. Rizvi
Discontinued for AE
a

n = 8 (18%)
Discontinued for PD
n = 7 (16%)
Patients on Pembro as of
Data Lock of March 3, 2014
n = 25 (56%)
a
Only 2 patients discontinued for treatment-related AEs.
Analysis cut-off date: March 3, 2014.
Total (N = 45)
Time on therapy, days,
mean (range)
154 (1-400)
Number of doses, median
(range)
9 (1-23)
-100
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Series 1
Maximum Percent Change from Baseline in Tumor
Size in Evaluable Patients
a
(Central Review, RECIST v1.1)
Analysis cut-off date: March 3, 2014.
a
Evaluable patients were those with measurable disease at baseline per central review who had ≥1 post baseline tumor assessment.

Presented by: Naiyer A. Rizvi
10 mg/kg Q3W
10 mg/kg Q2W
2 mg/kg Q3W
*
Still on treatment
*
*
* * *
*
*
*
*
*
*
*
* *
* *
*
*
*
*
*
Antitumor Activity by Pembrolizumab Dose
Pembro
Dose
RECIST v1.1, Central Review
a
irRC, Investigator Review
n
ORR
b
DCR
b

n
ORR
b
DCR
b

n (%)
[95% CI]
n (%)
[95% CI]
n (%)
[95% CI]
n (%)
[95% CI]
2 mg/kg
Q3W
6 2 (33%)
[4%-78%]
3 (50%)
[12%-88%]
6 4 (67%)
[22%-96%]
5 (83%)
[36%-100%]
10 mg/kg
Q3W
20 4 (20%)
[6%-44%]
14 (70%)
[46%-88%]
22 10 (46%)
[24%-68%]
18 (82%)
[60%-95%]
10 mg/kg
Q2W
16 5 (31%)
[11%-59%]
10 (63%)
[35%-85%]
17 7 (41%)
[18%-67%]
12 (71%)
[44%-90%]
Total 42 11 (26%)
[14%-42%]
27 (64%)
[48%–78%]
45 21 (47%)
[32%-62%]
35 (78%)
[63%-89%]
Presented by: Naiyer A. Rizvi
Analysis cut-off date: March 3, 2014. DCR = Disease control rate (complete response + partial response + stable disease)
a
3 patients did not have measurable disease by RECIST v1.1 per independent central review at baseline and were not evaluated for response by RECIST v1.1.

b
Includes confirmed and unconfirmed responses.
c
From product-limit (Kaplan-Meier) method for censored data.
• Interim median PFS
c
:
• 27.0 weeks (95% CI, 13.6-45.0) by RECIST v1.1 per central review
• 37.0 weeks (95% CI, 27.0-NR) by irRC per investigator review
Time to and Durability of
Response
a

a
Includes confirmed and unconfirmed responses.
b
Includes 2 responders who showed progressive disease at the most recent tumor assessment but remain on therapy pending
confirmation of disease progression.

Bars represent the relative number of weeks from first pembro dose to progressive disease (PD) or last non-PD assessment.
Analysis cut-off date: March 3, 2014.
Presented by: Naiyer A. Rizvi
• 11 of 11 (100%) responses are ongoing
– Median duration of response not reached (median
follow-up, 36 weeks)
• 7 of 11 (64%) responders remain on treatment
– Median duration of treatment: 27.1 weeks (range,
15.0+ – 48.3+)
• 19 of 21 (90%) responses are ongoing
– Median duration of response not reached (median
follow-up, 36 weeks)
• 18 of 21 (86%) responders remain on treatment
b
– Median duration of treatment: 27.1 weeks
(range, 6.1 – 57.1+)
RECIST v1.1
Central Review
0 10 20 30 40 50
Time, weeks
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irRC
Investigator Review
0 10 20 30 40 50 60
Time, weeks
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Pembro 2 mg/kg Q3W
Pembro 10 mg/kg Q3W
Pembro 10 mg/kg Q2W
Partial Response
Progression
On Treatment
Treatment-Related Adverse Event Profile
Treatment-Related
Adverse Event, n (%)
Total
N = 45
Any 36 (80%)
Fatigue 10 (22%)
Pruritus 6 (13%)
Hypothyroidism 4 (9%)
Dermatitis acneiform 3 (7%)
Diarrhea 3 (7%)
Dyspnea 3 (7%)
Rash 3 (7%)
Presented by: Naiyer A. Rizvi
AEs of Any Grade,
Incidence >5%
Analysis cut-off date: March 3, 2014.
• Specific AE terms listed are
grade 1-2 only
Treatment-Related
Adverse Event, n (%)
Total
N = 45
Resulted in
Discontinuation
Blood creatine
phosphokinase
increased (Gr 4)
1 (2%) No
Pericardial effusion
(Gr 3)
1 (2%) No
Pneumonitis (Gr 3) 1 (2%) Yes
Acute kidney injury
(Gr 2)
1 (2%) Yes
Grade 3-4 AEs or
AEs Leading to Discontinuation
Courtesy of L. Gandhi, AACR 2014, Abstract CT105.
Response Rate by RECIST v1.1 (Central Review)
and by irRC (Investigator-Assessed) with PD-L1
Clinical Trial Assay
a
19%
37%
15%
7%
0
10
20
30
40
50
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%

RECIST v1.1
Total (N = 129) PS ≥50% (n = 41)
PS 1-49% (n = 46) PS 0% (n = 42)
RR = Response rate (confirmed and unconfirmed complete and partial response).
PS=Proportion score. Strong PD-L1 positive staining was considered ≥50% of tumor cells, and weak was defined as staining between 1-49% of positively staining tumor cells.
Negative had no tumor staining for PD-L1.
Data cut-off: December 31, 2013.
a
Evaluable patients were those patients in the training set with evaluable tumor PD-L1 expression who had measurable disease at baseline
per imaging assessment criteria.
19%
45%
8%
8%
0
10
20
30
40
50
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p
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R
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%

irRC
Total (N = 146) PS ≥50% (n = 44)
PS 1-49% (n = 53) PS 0% (n = 49)
Conclusions
• Pembrolizumab has an acceptable and manageable toxicity profile
• Pembrolizumab provides robust antitumor activity as first-line therapy for PD-L1
+
NSCLC
a

– 26% ORR by RECIST, 47% by irRC
– 100% of responders by RECIST and 90% of responders by irRC remain in response (median duration
of response not reached)
– 64% of responders by RECIST and 86% of responders by irRC remain on treatment
– 27-week median PFS by RECIST, 37 weeks by irRC
• An additional 50 PD-L1
+
, treatment-naïve patients are enrolled in KEYNOTE-001 as part of the
biomarker validation set
– At final analysis, total population will be analyzed using the 50% cutpoint with the
clinical trial assay
• KEYNOTE-024
– Phase 3 study that will compare pembrolizumab monotherapy to platinum-based doublet chemotherapy
in treatment-naïve patients with PD-L1
+
metastatic NSCLC
– Recruitment to begin in September 2014
• KEYNOTE-010 (abstract TPS8124 presented on May 31 by RS Herbst)
– Phase 2/3 study that will compare two doses of pembrolizumab to docetaxel in previously-treated
patients with NSCLC
Presented by: Naiyer A. Rizvi
a
Proportion score ≥1% by prototype assay.
First Presentation - Head & Neck

Tanguy Seiwert, MD
Assistant Professor of Medicine
Associate Director Head and Neck Cancer Program
Fellow, Institute of Genomics and Systems Biology
The University of Chicago
A Phase Ib Study of Pembrolizumab (MK-3475) in
Patients with HPV-negative and HPV-positive Head
& Neck Cancer
Presented by:
Tanguy Seiwert, MD
Assistant Professor of Medicine
Associate Director Head and Neck Cancer Program
Fellow, Institute for Genomics and Systems Biology
The University of Chicago
Tanguy Seiwert, Barbara Burtness, Jared Weiss, Iris Gluck, J. Paul Eder, Sara I.
Pai, Marisa Dolled-Filhart, Kenneth Emancipator, Kumudu Pathiraja, Christine
Gause, Robert Iannone, Holly Brown, Jennifer Houp, Jonathan Cheng, Laura Q.
Chow
Disclosures

• Study supported by Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co, Inc., Whitehouse
Station, NJ

• Tanguy Seiwert
– Research Funding: Genentech, Boehringer-Ingelheim
– Honoraria: Novartis, Bayer/Onyx

Presented by: Tanguy Seiwert
Background
• Head and neck squamous cell cancer (HNSCC) is the 5
th
most
common cancer worldwide

• Recurrent/metastatic HNSCC remains poorly treatable with a
median OS of 13 months
– Commonly used agents include platinum, taxanes, 5-FU, methotrexate,
cetuximab

• Prominent immune escape in HNSCC (Saloura et al, Lyford-Pike et al)
– T-cell inflamed phenotype (TILs + PD-L1 expression)
– Present in both HPV(-) and HPV(+)
– HPV related “foreign” antigens present in HPV(+) tumors


 Blocking PD1 interaction with its ligands PD-L1 or PD-L2 may
reactivate the immune surveillance and elicit anti-tumor activity.


Presented by: Tanguy Seiwert
Saloura et al ASCO 2014, Lyford-Pike et al Cancer Res 2013
HNSCC commonly triggers Immune
Responses: Tumor Infiltrating Lymphocytes
Presented by: Tanguy Seiwert
In Preparation: Imanguli /Seiwert 2014
Diffuse infiltration with CD8+ TILs in HNSCC Absence of TILs in HNSCC
“Mesenchymal” Subtype Shows High Degree of
CD8 TILs for Both HPV(+) and HPV(-) HNSCC
Presented by: Tanguy Seiwert
In Press: Keck et al 2014
Chicago HNC Genomics Cohort (CHGC) TCGA HNC
7-
8-
9-
12-
8-
4-
0-
C
D
8

m
R
N
A

e
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p
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s
s
i
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n

Basal
Classical
HPV
Mesenchymal
HPV
Basal
Classical
HPV
Mesenchymal
HPV
Mesenchymal
nonHPV

Classical
nonHPV

Mesenchymal
nonHPV

Classical
nonHPV

Basis for Immune therapy – Immune Escape
Presented by: Tanguy Seiwert
Melero I et al. Clin Cancer Res 2013;19:997-1008

• Expression of PD-L1
on
a) tumor cells &
b) macrophages
can suppress immune
surveillance.

• In mouse models
antibodies blocking
PD-1 / PD-L1
interaction lead to
tumor rejection


• Clinical prognosis
correlates with
presence of TILs and
PD-L1 expression in
multiple cancers.
Pembrolizumab (formerly: MK-3475)
• High-affinity monoclonal anti-PD1 antibody
• Humanized IgG4/kappa isotype
– no ADCC (non-depleting)
• Dual PD1-ligand blockade
– PD-L1 (B7H1)
– PD-L2 (B7DC)
• Antitumor activity seen in melanoma (under FDA
review) and NSCLC (Phase III testing)
 Durability of responses  long-term survival

Presented by: Tanguy Seiwert
KEYNOTE-012 – Study Design
• Multi-center, non-randomized Phase Ib HNSCC expansion
cohort
• Multi-cohort trial*  HNSCC cohort










*Additional cohorts included: Bladder Cancer, Triple Negative Breast Cancer, Gastric Cancer
Presented by: Tanguy Seiwert

Objectives
Primary:
1. Safety and tolerability in HNSCC patients
– Pre-specified Endpoint: Immune mediated AEs

2. To evaluate anti-tumor activity in PD-L1 positive
HPV(-) and HPV(+) HNSCC
– Response by RECIST 1.1
– Central radiology review (in process)

Secondary:
• Evaluate progression-free survival, overall survival
• Investigate biomarkers in tumors and blood

Presented by: Tanguy Seiwert
Eligibility
• Recurrent, metastatic, or persistent HNSCC
• HPV (-) or (+)
• ≥1% PD-L1 IHC expression in tumor cells or stroma (from an
archival or fresh tumor specimen)
• Measurable disease (RECIST 1.1)
• ECOG 0-1
• Adequate organ function
• Tumor tissue for biomarker analysis
• No autoimmune diseases
• No immunodeficiency or immunosuppressive therapy
• No viral infection (HIV, Hepatitis B/C)
• No active CNS disease
• No interstitial lung disease
• No active infection

Presented by: Tanguy Seiwert
Patient Overview
Presented by:

Head and Neck Cancer
(HPV Negative & Positive)

n %
Subjects dosed in population 60 100
Gender
Male 49 81.7
Female 11 18.3
Age (Years)
<65 34 56.7
≥65 26 43.3
Race
Asian 1 (1.7)
Black Or African American 6 (10.0)
Multi-Racial 1 (1.7)
White 52 (86.7)
Ethnicity
Hispanic Or Latino 1 (1.7)
Not Hispanic Or Latino 57 (95.0)
Unknown 2 (3.3)
ECOG
[0] Normal Activity 19 31.7
[1] Symptoms, but ambulatory 40 66.7
Unknown 1 1.7
Prior Lines of Therapy for Recurrent/Metastatic Disease
0 7 11.7
1 8 13.3
2 20 33.3
3 or more 22 36.7
Unknown 3 5.0
Prior Systemic Therapy for Locally Advanced Disease
Yes 25 41.7
No 32 53.3
Unknown 3 5.0
PD-L1 IHC Pre-screening of KEYNOTE 12 HNSCC
Tumor Samples
Presented by: Tanguy Seiwert
PD-L1Negative
 Ineligible
PD-L1-Tumor
Positive (weak)
PD-L1-Stroma
Positive
• Pre-Screening: IHC staining for PD-L1 using the Merck proprietary
22C3 antibody (CLIA); performed centrally
• A minimum of 1% tumor cells stained or uptake in stroma was
considered positive => eligible for treatment
PD-L1-Tumor
Positive (strong)
PD-L1 Screening Results
Presented by:
104 Patients screened:

PD-L1 Staining in Tumors of Screened Patients (N = 104)
Staining (%) 0 1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100
n 26* 24 8 9 3 2 2 4 3 2 21

Central confirmation
of HPV status pending.
PD-L1 positive: 78% (81)
• Study Eligible n = 61
*
• HPV (-) n = 36


• HPV (+) n = 23


• HPV (na) n = 2

PD-L1 negative: 22% (23)
Distribution of PD-L1 Positive Results
in Enrolled Patients:
*3 Pts with tumor (-)
but stroma (+) IHC
0
2
4
6
8
10
12
14
16
0 1 2 5 10 20 30 50 60 70 80 90 100
Tumor Cell Staining (%)
N
u
m
b
e
r

o
f

P
a
t
i
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n
t
s

(
n
)

HPV (-)
HPV (+)
Summary of Drug-related Adverse Events
Incidence > 5%*
Presented by: Tanguy Seiwert
All Grades Grades 3-5
n % n %
Any drug-related event 35 58.3 10 16.7
Fatigue 10 16.7 0 0.0
Pruritus 6 10.0 0 0.0
Rash 5 8.3 2 3.3
Nausea 4 6.7 0 0.0
Decreased appetite 3 5.0 0 0.0
Myalgia 3 5.0 0 0.0
*as of May 23, 2014
Pre-specified Adverse Events*
Presented by: Tanguy Seiwert
Adverse event n (%) Grade
Adrenal insufficiency 1 (1.7%) 2
Diarrhea 1 (1.7%) 3


Pruritus 1 (1.7%) 2
Rash 2 (3.3%) 2, 3
Rash, macular 1 (1.7%) 3
Pneumonitis 0 (0.0%) ---
ALT increase 2 (3.3%) 3, 3
AST increase 2 (3.3%) 2, 3
Total 10 (16.6%) ---

Patient continued on study, and no steroid treatment was initiated as diarrhea was self-limited
*as of May 23, 2014
Efficacy: Waterfall Plot*
Presented by: Tanguy Seiwert
51% (26/51) of patients had decreased tumor burden
HPV (+)
HPV (-)
Subjects
–100
–80
–60
–40
–20
0
20
40
60
80
100
C
h
a
n
g
e

F
r
o
m

B
a
s
e
l
i
n
e
,

%

 Best percent change from baseline in target lesions (site assessment) delineated by HPV status

*as of May 23, 2014; Includes only patients with RECIST measurable lesions at baseline and at least 1 follow-up scan
(n=51)
Best Overall Response*
Presented by: Tanguy Seiwert
56 pts evaluable for
Response
Total Head/neck
N=56

HPV (+)
N=20
HPV (-)
N=36
§
Response Evaluation n (%) 95% CI

n (%) 95% CI

n (%) 95% CI


Complete Response
1 (1.8) (0.0, 9.6)
1 (5.0) (0.1, 24.9) 0 (0.0) (0.0, 9.7)
Partial Response
10 (17.9) (8.9, 30.4)
3 (15.0) (3.2, 37.9) 7 (19.4) (8.2, 36.0)
Best Overall Response
(Complete + Partial)

11 (19.6) (10.2, 32.4) 4 (20.0) (5.7, 43.7) 7 (19.4) (8.2, 36.0)
Stable Disease
16 (28.6) (17.3, 42.2)
8 (40.0) (19.1, 63.9) 8 (22.2) (10.1, 39.2)
Progressive Disease
25 (44.6) (31.3, 58.5)
7 (35.0) (15.4, 59.2) 18 (50.0) (32.9, 67.1)
No Assessment
4 (7.1) (2.0, 17.3)
1 (5.0) (0.1, 24.9) 3 (8.3) (1.8, 22.5)
Based on RECIST 1.1 Per site assessment; includes confirmed and unconfirmed responses

61 patients eligible for treatment; 60 patients dosed; 56 patients eligible for pre-defined full analysis set.

A single patient with PD followed by PR on treatment was classified as PR.
§
Includes 2 patients for whom HPV data unavailable.

Based on binomial exact confidence interval method.
• PD-L1 expression correlates with Response
• Using a Youden-Index derived, preliminary PD-L1 cut point:
 Above cutpoint: 45.5% (5/11) RR
 Below cutpoint: 11.4% (5/44) RR
*as of May 23, 2014
Time on treatment and disposition*
Presented by: Tanguy Seiwert
Swimmer plot of all patients who experienced CR or PR.
 8 additional patients had SD >6 months, of which 7/8 remain on treatment.
0 4 8 12 16 20 24 28 32 36 40 44 48
Treatment Exposure, weeks
S
u
b
j
e
c
t
s

Complete Response
Partial Response
Treatment Ongoing
*as of May 23, 2014
Presented by:
Baseline Cycle 4 -28.3% Cycle 8 -56.1%

Wk 8 SD
Wk 16 PR
Patient Response (central review)
Presented by: Tanguy Seiwert
Summary / Conclusions
• Treatment with Pembrolizumab (MK-3475) is well tolerated
and safe in patients with HNSCC
– No serious drug related AEs to date
• PD-L1 expression in 78% of HNSCC (1% cutoff + stroma staining)
– PD-L1 expression is variable – with a bimodal distribution
– PD-L1 expression appears to correlate with response

• Preliminary evidence of efficacy in both HPV(-) and
HPV(+) HNSCC
– Many patients continue on treatment with SD/tumor shrinkage that
do not meet RECIST criteria for response at the time of this report
– Survival data is pending
• A Phase III study is planned for Q3 2014
Presented by: Tanguy Seiwert
Acknowledgments
The study team at Merck:
– Jonathan Cheng
– Christine Gause
– Robert Iannone
– Kumudu Pathiraja
– Marisa Dolled-Filhart
– Kenneth Emancipator
– Holly Brown
– Jennifer Houp
– Ed Gonzalez
– Ed O’Neill

Presented by: Tanguy Seiwert
Participating Centers / PIs:
• Laura Q. Chow (Univ. of Washington)
• Barbara Burtness (Fox Chase / Yale)
• Jared Weiss (UNC)
• Iris Gluck (Sheba)
• J. Paul Eder (Yale)
• Sara I. Pai (Johns Hopkins/MGH)


Additional Acknowledgements:
• Rita Nanda, Vicki Villaflor, Jonas de Souza,
Everett Vokes (Univ. of Chicago)
• Frank Worden (Univ. of Michigan)
• Alain Algazi (UCSF)


All patients and their families
Harnessing Immune Mechanisms in Oncology
Roy D. Baynes
Senior Vice President
Global Clinical Development
Merck Research Laboratories
Merck Immuno-Oncology Pipeline
REGISTRATION PHASE 1/2 PRECLINICAL
C
O
M
B
I
N
A
T
I
O
N



Other
antagonists



Anti-LAG3
RCC with pazopanib (GSK) (KN018)
RCC with axitinib (PFE)
HER2+ breast with trastuzumab
Solid tumors with 41BB (PFE)
MM with lenalidomide &
dexamethasone
Melanoma with IPI/Sylatron (KN029) Melanoma with T-VEC (AMGN)
NSCLC with abraxane (KN026)
NSCLC with chemo, IPI, & TKI (KN021)
Phase 3 Melanoma IPI naïve (KN006)
Phase 2 Melanoma IPI refractory
(KN002)
Phase 2/3 NSCLC (KN010)
Phase 3 Head & neck
Phase 3 Bladder
Phase 3 Melanoma adjuvant
Phase 3 NSCLC 1st line (KN024)
Biomarker +
20 multiple
solid tumors
(KN028)
Melanoma & NSCLC (KEYNOTE001)
Head & neck, bladder, triple neg breast & gastric (KN012)
Hematologic malignancies (KN013)
MSI-high Colerectal and noncolon (KN016)
Melanoma brain metastasis (KN027)
M
O
N
O
T
H
E
R
A
P
Y

Ongoing
Planned
STUDIES
Anti-GITR (MK-4166): Solid tumors
Melanoma BRAF & MEK Inh (GSK)
(KN022)
NSCLC with IDO1 (INCY)
KN = Keynote.


Other
agonists



What to Expect in Immuno-Oncology in 2014
• Anticipated approval in advanced melanoma in US
• Filing for advanced melanoma in EU
• 3 additional registration trials to begin
– First registration studies in 2 new tumor types: head & neck and bladder
– Registration study in adjuvant melanoma
• 4 additional combination trials to begin in melanoma, NSCLC and solid
tumors
– In combination with standard of care, immunotherapies, and emerging
approaches
• Proof of concept in other tumor types
• Anti-GITR clinical study initiation
Q&A
Adam H. Schechter
Executive Vice President and President
Global Human Health
Tanguy Seiwert, MD
Assistant Professor of Medicine
The University of Chicago
Roy D. Baynes
SVP, Global Clinical Development
Merck Research Laboratories
Roger M. Perlmutter
Executive Vice President and President
Merck Research Laboratories