MRK ASCO Investor Briefing

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 Mercks 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; Mercks ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Mercks 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 Mercks 2013 Annual Report on Form 10-K and the companys other filings with the Securities and Exchange Commission (SEC) available at the SECs 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 1st 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

Mercks 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 Nave 10 mg/kg Q2W

(n = 41)


(n = 24)


(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 Nave 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 Sizea (Central Review, RECIST v1.1)


aIn patients w ith 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

0

20

40

60

80

100

Cha

nge F

rom

Bas

elin

e in

Sum

of

Long

est D

iam

eter

of T

arge

t Les

ion,

%

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


aAssessed by independent central review in patients w ith measurable disease by RECIST v1.1 by central review at baseline. bAssessed by investigator review. Analysis cut-off date: October 18, 2013.

N CR, % ORR, %

(95% CI)

RECIST v1.1a

IPI-N 168 8 40 (32-48)

IPI-T 197 2 28 (22-35)

Total 365 5 34 (29-39)

irRCb

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)


aOngoing 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

Indi

vidu

al P

atie

nts

Trea

ted

With

Pem

brol

izum

ab

12 months 6 months 18 months

88% of responses ongoinga Median response duration

not reached (range, 6+ to 76+ weeks)

Kaplan-Meier Estimate of Overall Survival


aOS 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 monthsa

Ove

rall

Surv

ival

, %

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


Adverse Event, %

Total N = 411

Any Grade Grade 3/4 Fatigue 36 2 Pruritus 24

Summary Overall, 34% ORR (RECIST v1.1, central review)

40% ORR in IPI-N patients 44% ORR in treatment-nave 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


NSCLC Highlights


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


Discontinued for AEa n = 8 (18%)

Discontinued for PD n = 7 (16%)

Patients on Pembro as of Data Lock of March 3, 2014

n = 25 (56%)

aOnly 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

-80

-60

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Axi

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Series 1

Maximum Percent Change from Baseline in Tumor Size in Evaluable Patientsa (Central Review, RECIST v1.1)

Analysis cut-off date: March 3, 2014. aEvaluable patients were those with measurable disease at baseline per central review who had 1 post baseline tumor assessment.


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 Reviewa irRC, Investigator Review

n

ORRb DCRb

n

ORRb DCRb

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%]


Analysis cut-off date: March 3, 2014. DCR = Disease control rate (complete response + partial response + stable disease) a3 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. bIncludes confirmed and unconfirmed responses. cFrom product-limit (Kaplan-Meier) method for censored data.

Interim median PFSc: 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 Responsea

aIncludes confirmed and unconfirmed responses. bIncludes 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.


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 treatmentb

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

Indi

vidu

al P

atie

nts

Trea

ted

With

Pem

bro

irRC Investigator Review

0 10 20 30 40 50 60 Time, weeks

Indi

vidu

al P

atie

nts

Trea

ted

With

Pem

bro

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%)


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 Assaya

19%

37%

15%

7%

0

10

20

30

40

50

Resp

onse

Rat

e, %

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. aEvaluable patients were those patients in the training set w ith 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

Resp

onse

Rat

e, %

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+ NSCLCa 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-nave 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-nave 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


aProportion 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 5th 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.


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-

CD

8 m

RN

A ex

pres

sion

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


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


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


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


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)

PD-L1 IHC Pre-screening of KEYNOTE 12 HNSCC Tumor Samples


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 (%)

Num

ber

of P

atie

nts

(n) HPV (-) HPV (+)

Summary of Drug-related Adverse Events Incidence > 5%*


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*


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*


51% (26/51) of patients had decreased tumor burden

HPV (+) HPV (-)

Subjects 100

80

60

40

20

0

20

40

60

80

100

Cha

nge F

rom

Bas

elin

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*


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*


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

Subj

ects

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)


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


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 ONeill


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


Merck Immuno-Oncology Pipeline

REGISTRATION PHASE 1/2 PRECLINICAL

CO

MB

INAT

ION

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 nave (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)

MO

NO

THER

APY

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

Merck ASCO 2014 Investor BriefingForward-Looking StatementAgendaMerck ASCO 2014 Investor BriefingMercks Strategy in Immuno-OncologyAdvanced Melanoma Highlights411 Patients in Melanoma Expansion Cohorts: KEYNOTE-001Maximum Percent Change from Baseline in Tumor Sizea (Central Review, RECIST v1.1)Antitumor Activity by Prior Ipilimumab and Pembrolizumab Dose/ScheduleSlide Number 10Kaplan-Meier Estimate of Overall Survival Treatment-Related AEs With Incidence >5%SummaryNSCLC HighlightsKEYNOTE-001: PD-L1 Expression in Previously Untreated NSCLCKEYNOTE-001: Patient DispositionMaximum Percent Change from Baseline in Tumor Size in Evaluable Patientsa (Central Review, RECIST v1.1)Antitumor Activity by Pembrolizumab DoseTime to and Durability of Responsea Treatment-Related Adverse Event ProfileResponse Rate by RECIST v1.1 (Central Review) and by irRC (Investigator-Assessed) with PD-L1 Clinical Trial AssayaConclusionsFirst Presentation - Head & NeckA Phase Ib Study of Pembrolizumab (MK-3475) in Patients with HPV-negative and HPV-positive Head & Neck CancerDisclosuresBackgroundHNSCC commonly triggers Immune Responses: Tumor Infiltrating LymphocytesMesenchymal Subtype Shows High Degree of CD8 TILs for Both HPV(+) and HPV(-) HNSCCBasis for Immune therapy Immune EscapePembrolizumab (formerly: MK-3475)KEYNOTE-012 Study DesignObjectivesEligibilityPatient OverviewPD-L1 IHC Pre-screening of KEYNOTE 12 HNSCC Tumor SamplesPD-L1 Screening ResultsSummary of Drug-related Adverse Events Incidence > 5%*Pre-specified Adverse Events*Efficacy: Waterfall Plot*Best Overall Response* Time on treatment and disposition*Slide Number 42Slide Number 43Summary / ConclusionsAcknowledgmentsHarnessing Immune Mechanisms in OncologyMerck Immuno-Oncology PipelineWhat to Expect in Immuno-Oncology in 2014Q&A

Documents

MRK ASCO Investor Briefing