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March 7, 2018 5:05 pm ET

Companies to Jointly Develop and Commercialize LENVIMA, as Monotherapy and in Combination with Merck’s KEYTRUDA ^® (pembrolizumab) for Multiple Cancer Types

Eisai Books LENVIMA Product Sales and Companies to Share Development and Marketing Costs Equally, as well as Gross Profits From LENVIMA

LENVIMA/KEYTRUDA Combination Already Granted U.S. FDA Breakthrough Therapy Designation for Renal Cell Carcinoma; Expanded Joint Development Program to Support 11 Additional Potential Indications Across Six Other Cancer Types

Merck’s Strong Commercial Footprint and Medical Expertise, Combined with Eisai’s Extensive Real-World Evidence for LENVIMA, Will Expedite Patient Access Worldwide for Current and Future Potential Indications

Eisai Co., Ltd. and Merck (NYSE:MRK), known as MSD outside the United
States and Canada, today announced that the companies have agreed upon a
strategic collaboration for the worldwide co-development and
co-commercialization of LENVIMA^® (lenvatinib mesylate), an
orally available tyrosine kinase inhibitor discovered by Eisai. Under
the agreement, Eisai and Merck will develop and commercialize LENVIMA
jointly, both as monotherapy and in combination with Merck’s anti-PD-1
therapy, KEYTRUDA^® (pembrolizumab).

Eisai will book LENVIMA product sales globally, as monotherapy and in
combination, and Merck and Eisai will share gross profits equally.
LENVIMA is currently approved as monotherapy for use in the treatment of
thyroid cancer, as well as in combination with everolimus for the
treatment of patients with renal cell carcinoma (RCC) who have failed
previous therapy. Applications for regulatory approval of LENVIMA
monotherapy for the treatment of hepatocellular carcinoma have been
submitted in Japan, the United States, Europe, China and other countries.

A Phase 3 study (Study 307), sponsored by Eisai, is ongoing to evaluate
separate combinations of LENVIMA with KEYTRUDA (pembrolizumab) or
LENVIMA with everolimus versus chemotherapy alone for the treatment of
RCC. In January 2018, the companies announced that the U.S. Food and
Drug Administration (FDA) granted Breakthrough Therapy Designation for
the LENVIMA/KEYTRUDA combination in advanced and/or metastatic RCC. This
was based on interim results from an ongoing Phase 1b/2 trial (Study
111/KEYNOTE-146), evaluating the combination in select solid tumors
(including RCC and endometrial cancer), which provided evidence for
synergistic effects on the observed overall response rate, regardless of
treatment experience or PD-L1 tumor expression.

Per the agreement, the companies will also jointly initiate new clinical
studies evaluating the LENVIMA/KEYTRUDA combination to support 11
potential indications in six types of cancer (endometrial cancer,
non-small cell lung cancer, hepatocellular carcinoma, head and neck
cancer, bladder cancer and melanoma), as well as a basket trial
targeting multiple cancer types.

“Aiming to maximize the potential of LENVIMA and expedite the creation
of innovative treatments in this age of “Cancer Evolution,” we have
entered into this collaboration with Merck who developed the anti-PD-1
antibody KEYTRUDA,” commented Haruo Naito, Representative Corporate
Officer and CEO of Eisai Co., Ltd. “By providing new treatment options
including for refractory cancers with no hopes for a cure to date, we
are striving to further contribute to increasing the benefits provided
to patients and their families.”

“Together with Eisai, we aim to maximize the value of LENVIMA for its
current indications while jointly pursuing additional approvals in
combination with KEYTRUDA across a wide range of cancers,” said Dr.
Roger M. Perlmutter, President, Merck Research Laboratories. “There is
strong scientific evidence supporting synergistic effects of KEYTRUDA
when used in combination with LENVIMA, and the companies have already
received Breakthrough Therapy Designation from the U.S. FDA for the
KEYTRUDA/LENVIMA combination in renal cell carcinoma. Through this
collaboration, we will both broaden our oncology portfolio and have the
opportunity to help even more cancer patients around the world.”

Financial Considerations

Gross profits from LENVIMA product sales globally will be shared equally
by Eisai and Merck. Expenses incurred during co-development, including
for studies evaluating LENVIMA as monotherapy, will be shared equally by
the two companies.

Under the agreement, Merck will pay Eisai an upfront payment of $300
million U.S. dollars and up to $650 million U.S. dollars for certain
option rights through 2020 (Eisai’s financial year: fiscal year ended
March 2021), as well as $450 million U.S. dollars as reimbursement for
research and development expenses. In addition, Eisai is eligible to
receive up to $385 million U.S. dollars associated with the achievement
of certain clinical and regulatory milestones and a maximum of up to
$3.97 billion U.S. dollars for the achievement of milestones associated
with sales of LENVIMA. Assuming the achievement of all development and
commercial goals for all indications, the total amount of upfront,
option and regulatory and sales milestone payments has the potential to
reach up to $5.76 billion U.S. dollars.

The impact of this collaboration on Eisai’s consolidated financial
results has been incorporated into the Notification Regarding Revision
of Consolidated Financial Results Forecasts (IFRS) for the Fiscal Year
Ending March 31, 2018 announced on March 8 (Japan).

About the Phase 1b/2 Study (Study 111/KEYNOTE-146) that Supported
Breakthrough Therapy Designation for the LENVIMA/KEYTRUDA Combination

Study 111/KEYNOTE-146 is a multicenter, open-label, Phase 1b/2 clinical
study being carried out in the United States and the European Union to
evaluate the efficacy and safety of LENVIMA in combination with KEYTRUDA
(pembrolizumab). The primary objective of the Phase 1b portion of the
study was to determine the maximum tolerated dose in patients with
unresectable solid tumors (endometrial cancer, melanoma, non-small cell
lung cancer, RCC, squamous cell carcinoma of the head and neck, and
urothelial cancer) who had progressed after treatment with approved
therapies or for which there are no standard effective therapies
available. The initial part of Phase 2 enrolled patients with select
solid tumors after previous treatment with 0-2 lines of systemic therapy
(unless discussed with the sponsor) with a recommended dosage based on
the results of the Phase 1b part. The primary endpoint of the initial
part of Phase 2 was objective response rate (ORR) after 24 weeks of
treatment, with select secondary endpoints including ORR, disease
control rate, progression-free survival, and duration of response. The
expansion part of Phase 2 is ongoing, and enrollment of patients is
continuing in the endometrial cancer cohort.

From the results of the analysis (investigator review) of the RCC cohort
1 (n=30) in Study 111/KEYNOTE-146 as of March 1, 2017, the primary
endpoint of the Phase 2 portion, ORR after 24 weeks of treatment (ORR
Week 24) was 63 percent (95% CI, 44-80), with tumor regression observed
in 93 percent (28/30) of patients since the initiation of treatment
(baseline). A tumor response was observed regardless of previous
treatment experience or tumor PD-L1 expression. In this cohort, the most
frequently observed adverse events (top six) were diarrhea, fatigue,
hypothyroidism, stomatitis, hypertension, and nausea.

The results of the interim analysis (n=23) of the endometrial cancer
cohort in Study 111/KEYNOTE-146 as of December 1, 2016, indicated ORR
Week 24 of 52.2 percent (95% CI, 30.6-73.2) based on independent
radiologic review and 47.8 percent (95% CI, 26.8-69.4) based on
investigator review. Additionally, tumor regression was observed
regardless of the state of microsatellite instability (MSI). Anti-PD-1
antibodies are generally less effective in patients with low frequency
of MSI, which is a biomarker for the inability to repair errors in the
base sequence of DNA, or who are MSI negative. In this cohort, the most
frequently observed adverse events (top five) were hypertension,
fatigue, arthralgia, diarrhea, and nausea.

Meanwhile, a similar Phase 1b clinical study (Study 115/KEYNOTE-523) in
Japanese patients with unresectable solid tumors and a Phase 1b clinical
study (Study 116/KEYNOTE-524) of the combination therapy in
hepatocellular carcinoma in Japan and the United States are both
underway.

About LENVIMA

^®

(lenvatinib mesylate)

Discovered and developed in-house by Eisai, LENVIMA is an orally
administered multiple receptor tyrosine kinase (RTK) inhibitor with a
novel binding mode that selectively inhibits the kinase activities of
vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and
VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2,
FGFR3 and FGFR4) in addition to other pathway-related RTKs (including
the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET)
involved in tumor angiogenesis, tumor progression and modification of
tumor immunity.

Currently, Eisai has obtained approval for LENVIMA as a treatment for
refractory thyroid cancer in over 50 countries, including the United
States, Japan, in Europe and Asia. Additionally, Eisai has obtained
approval for the agent in combination with everolimus as a second-line
treatment for RCC in over 40 countries, including the United States and
in Europe. In Europe, the agent was launched under the brand name Kisplyx^®
for RCC.

Furthermore, Eisai has submitted applications for an indication covering
hepatocellular carcinoma in Japan (June 2017), the United States and
Europe (July 2017), China (October 2017), Taiwan (December 2017) and
other countries.

The eight major clinical studies in progress on LENVIMA are as follows:

• A Phase 3 clinical study (Study 307) of separate combinations of
  LENVIMA with KEYTRUDA (pembrolizumab) or LENVIMA with everolimus
  versus chemotherapy alone in RCC (first-line) conducted in Japan, the
  United States and Europe.
• A Phase 3 clinical study (Study 308) of LENVIMA in thyroid cancer
  being conducted in China.
• A Phase 2 clinical study (Study 215) of LENVIMA in biliary tract
  cancer being conducted in Japan.
• A Phase 2 clinical study (Study 209) of LENVIMA in non-small cell lung
  cancer with RET translocations being conducted in Japan, the United
  States, Europe and Asia.
• A Phase 1b/2 clinical study (Study 111/KEYNOTE-146) of LENVIMA in
  combination with KEYTRUDA in select solid tumors (RCC, endometrial
  cancer, non-small cell lung cancer, urothelial cancer, squamous cell
  carcinoma of the head and neck, and melanoma) being conducted in the
  United States and European Union. Based on interim results, the
  combination treatment has been granted Breakthrough Therapy
  Designation by the U.S. FDA for the potential treatment of patients
  with advanced and/or metastatic RCC.
• A Phase 1b clinical study (Study 115/KEYNOTE-523) of LENVIMA in
  combination with KEYTRUDA in select solid tumors (RCC, endometrial
  cancer, non-small cell lung cancer, urothelial cancer, squamous cell
  carcinoma of the head and neck, and melanoma) being conducted in Japan.
• A Phase 1b clinical study (Study 116/KEYNOTE-524) of LENVIMA in
  combination with KEYTRUDA in hepatocellular carcinoma being conducted
  in Japan and the United States.
• A Phase 1b clinical study of LENVIMA in combination with nivolumab in
  hepatocellular carcinoma being conducted in Japan.

LENVIMA

^®

(lenvatinib) Indications in the U.S.

LENVIMA^® (lenvatinib) is a kinase inhibitor that is indicated
for:

• Differentiated Thyroid Cancer (DTC): single agent for patients with
  locally recurrent or metastatic, progressive, radioactive
  iodine-refractory DTC.
• Renal Cell Cancer (RCC): in combination with everolimus for patients
  with advanced RCC following one prior anti-angiogenic therapy.

Important Safety Information

Warnings and Precautions

• In DTC, hypertension was reported in 73% of patients on LENVIMA
  (lenvatinib) vs 16% with placebo (44% vs 4% grade ≥3). In RCC,
  hypertension was reported in 42% of patients on LENVIMA + everolimus
  vs 10% with everolimus alone (13% vs 2% grade 3). Serious
  complications of poorly controlled hypertension, including aortic
  dissection, have been reported. Systolic blood pressure ≥160 mmHg
  occurred in 29% of patients, and 21% of patients had a diastolic blood
  pressure ≥100 mmHg in the LENVIMA + everolimus–treated group. Blood
  pressure should be controlled prior to treatment and monitored
  throughout. Withhold dose for grade 3 hypertension despite optimal
  antihypertensive therapy; resume at reduced dose when controlled at
  grade ≤2. Discontinue for life-threatening hypertension
• In DTC, cardiac dysfunction was reported in 7% of patients on LENVIMA
  vs 2% with placebo (2% vs 0% grade ≥3). In RCC, decreased ejection
  fraction and cardiac failure were reported in 10% of patients on
  LENVIMA + everolimus vs 6% with everolimus alone (3% vs 2% grade 3).
  Monitor for signs/symptoms of cardiac decompensation. Withhold LENVIMA
  for development of grade 3 cardiac dysfunction until improvement to
  grade 0, 1, or baseline. Resume at reduced dose or discontinue based
  on severity and persistence of cardiac dysfunction. Discontinue for
  grade 4 cardiac dysfunction
• In DTC, arterial thromboembolic events were reported in 5% of patients
  on LENVIMA vs 2% with placebo (3% vs 1% grade ≥3). In RCC, arterial
  thromboembolic events were reported in 2% of patients on LENVIMA +
  everolimus vs 6% with everolimus alone (2% vs 4% grade ≥3).
  Discontinue following an arterial thrombotic event. The safety of
  resuming LENVIMA after an arterial thromboembolic event has not been
  established, and LENVIMA has not been studied in patients who have had
  an arterial thromboembolic event within the previous 6 months
• Across clinical studies in which 1,160 patients received LENVIMA
  monotherapy, hepatic failure (including fatal events) was reported in
  3 patients and acute hepatitis in 1 patient. In DTC, ALT and AST
  increases (grade ≥3) occurred in 4% and 5% of patients on LENVIMA,
  respectively, vs 0% with placebo. In RCC, ALT and AST increases (grade
  ≥3) occurred in 3% of patients on LENVIMA + everolimus vs 2% and 0%
  with everolimus alone, respectively. Monitor liver function before
  initiation, then every 2 weeks for the first 2 months, and at least
  monthly thereafter during treatment. Withhold dose for liver
  impairment grade ≥3 until resolved to grade 0, 1, or baseline. Resume
  at reduced dose or discontinue based on severity/persistence of
  hepatotoxicity. Discontinue for hepatic failure
• In DTC, proteinuria was reported in 34% of patients on LENVIMA vs 3%
  with placebo (11% vs 0% grade 3). In RCC, proteinuria was reported in
  31% of patients on LENVIMA + everolimus vs 14% with everolimus alone
  (8% vs 2% grade 3). Monitor for proteinuria before and during
  treatment. Withhold dose for proteinuria ≥2 g/24 h. Resume at reduced
  dose when proteinuria is <2 g/24 h. Discontinue for nephrotic syndrome
• In RCC, diarrhea was reported in 81% of patients on LENVIMA +
  everolimus vs 34% with everolimus alone (19% vs 2% grade ≥3). Initiate
  prompt medical management for the development of diarrhea. Monitor for
  dehydration. Withhold dose for diarrhea grade ≥3. Resume at a reduced
  dose when diarrhea resolves to grade 1 or baseline. Permanently
  discontinue LENVIMA for grade 4 diarrhea despite medical management
• In DTC, events of renal impairment were reported in 14% of patients on
  LENVIMA vs 2% with placebo (3% vs 1% grade ≥3). In RCC, events of
  renal impairment were reported in 18% of patients on LENVIMA +
  everolimus vs 12% with everolimus alone (10% vs 2% grade ≥3). Withhold
  LENVIMA for grade 3 or 4 renal failure/impairment. Resume at reduced
  dose or discontinue, depending on severity/persistence of renal
  impairment. Active management of diarrhea and any other
  gastrointestinal (GI) symptoms should be initiated for grade 1 events
• In DTC, events of GI perforation or fistula were reported in 2% of
  patients on LENVIMA vs 0.8% with placebo. In RCC, events of GI
  perforation, abscess, or fistula (grade ≥3) were reported in 2% of
  patients on LENVIMA (lenvatinib) + everolimus vs 0% with everolimus
  alone. Discontinue in patients who develop GI perforation or
  life-threatening fistula
• In DTC, QT/QTc interval prolongation was reported in 9% of patients on
  LENVIMA vs 2% with placebo (2% vs 0% >500 ms). In RCC, QTc interval
  increases >60 ms were reported in 11% of patients on LENVIMA +
  everolimus (6% >500 ms) vs 0% with everolimus alone. Monitor
  electrocardiograms in patients with congenital long QT syndrome,
  congestive heart failure, bradyarrhythmias, or patients taking drugs
  known to prolong the QT interval. Monitor and correct electrolyte
  abnormalities in all patients. Withhold dose for QTc interval
  prolongation >500 ms. Resume at reduced dose when QTc prolongation
  resolves to baseline
• In DTC, hypocalcemia (grade ≥3) was reported in 9% of patients on
  LENVIMA vs 2% with placebo. In RCC, hypocalcemia (grade ≥3) was
  reported in 6% of patients on LENVIMA + everolimus vs 2% with
  everolimus alone. Monitor blood calcium levels at least monthly and
  replace calcium as necessary. Interrupt and adjust LENVIMA as necessary
• Across clinical studies in which 1,160 patients received LENVIMA
  monotherapy, reversible posterior leukoencephalopathy syndrome (RPLS)
  was reported in 4 patients. Withhold LENVIMA for RPLS until fully
  resolved. Resume at reduced dose or discontinue based on the severity
  and persistence of neurologic symptoms
• Across clinical studies in which 1,160 patients received LENVIMA
  monotherapy, hemorrhage (grade ≥3) was reported in 2% of patients. In
  DTC, hemorrhagic events occurred in 35% of patients on LENVIMA vs 18%
  with placebo (2% vs 3% grade ≥3). There was 1 fatal intracranial
  hemorrhage case among 16 patients who received LENVIMA and had central
  nervous system metastases at baseline. The most frequently reported
  hemorrhagic event was epistaxis (11% grade 1, 1% grade 2).
  Discontinuation due to hemorrhagic events occurred in 1% of patients
  on LENVIMA. In RCC, hemorrhagic events occurred in 34% of patients on
  LENVIMA + everolimus vs 26% with everolimus alone (8% vs 2% grade ≥3).
  The most frequently reported hemorrhagic event was epistaxis (23% for
  LENVIMA + everolimus vs 24% with everolimus alone). There was 1 fatal
  cerebral hemorrhage case. Discontinuation due to hemorrhagic events
  occurred in 3% of patients on LENVIMA + everolimus. Consider the risk
  of severe or fatal hemorrhage associated with tumor
  invasion/infiltration of major blood vessels (eg, carotid artery).
  Withhold LENVIMA for the development of grade 3 hemorrhage until
  resolved to grade 0 or 1. Resume at reduced dose or discontinue based
  on severity/persistence of hemorrhage. Discontinue for grade 4
  hemorrhage
• In DTC patients with normal baseline thyroid-stimulating hormone
  (TSH), elevation of TSH level above 0.5 mU/L was observed postbaseline
  in 57% of patients on LENVIMA vs 14% with placebo. In RCC, grade 1 or
  2 hypothyroidism occurred in 24% of patients on LENVIMA + everolimus
  vs 2% with everolimus alone. In RCC patients with normal or low TSH at
  baseline, elevation of TSH was observed postbaseline in 60% of
  patients on LENVIMA + everolimus vs 3% with everolimus alone. Monitor
  thyroid function before initiation of and at least monthly throughout
  treatment. Treat hypothyroidism according to standard medical practice
  to maintain a euthyroid state
• Impaired wound healing, including fistula formation, has been reported
  in patients receiving LENVIMA. Temporary interruption of LENVIMA
  therapy should be considered in patients undergoing major surgical
  procedures
• LENVIMA can cause fetal harm when administered to a pregnant woman.
  Advise females of reproductive potential to use effective
  contraception during treatment with LENVIMA and for at least 2 weeks
  following completion of therapy

Adverse Reactions

• In DTC, the most common adverse reactions (≥30%) observed in
  LENVIMA-treated patients vs placebo-treated patients were hypertension
  (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs 17%),
  arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs 18%),
  weight decrease (51% vs 15%), nausea (47% vs 25%), stomatitis (41% vs
  8%), headache (38% vs 11%), vomiting (36% vs 15%), proteinuria (34% vs
  3%), palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal
  pain (31% vs 11%), and dysphonia (31% vs 5%)
• In DTC, adverse reactions led to dose reductions in 68% of patients
  receiving LENVIMA (lenvatinib) and in 5% of patients receiving
  placebo; 18% of patients discontinued LENVIMA and 5% discontinued
  placebo for adverse reactions. The most common adverse reactions
  (≥10%) resulting in dose reductions of LENVIMA were hypertension
  (13%), proteinuria (11%), decreased appetite (10%), and diarrhea
  (10%); the most common adverse reactions (≥1%) resulting in
  discontinuation of LENVIMA were hypertension (1%) and asthenia (1%)
• In RCC, the most common adverse reactions (>30%) observed in patients
  treated with LENVIMA + everolimus vs everolimus alone were diarrhea
  (81% vs 34%), fatigue (73% vs 40%), arthralgia/myalgia (55% vs 32%),
  decreased appetite (53% vs 18%), vomiting (48% vs 12%), nausea (45% vs
  16%), stomatitis/oral inflammation (44% vs 50%),
  hypertension/increased blood pressure (42% vs 10%), peripheral edema
  (42% vs 20%), cough (37% vs 30%), abdominal pain (37% vs 8%),
  dyspnea/exertional dyspnea (35% vs 28%), rash (35% vs 40%), weight
  decreased (34% vs 8%), hemorrhagic events (32% vs 26%), and
  proteinuria/urine protein present (31% vs 14%). The most common
  serious adverse reactions (≥5%) were renal failure (11%), dehydration
  (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting
  (5%), and dyspnea (5%)
• In RCC, adverse reactions led to dose reductions or interruption in
  89% of patients receiving LENVIMA + everolimus and in 54% of patients
  receiving everolimus alone. The most common adverse reactions (≥5%)
  resulting in dose reductions in the LENVIMA + everolimus–treated group
  were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting
  (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due
  to an adverse reaction occurred in 29% of patients in the
  LENVIMA + everolimus–treated group and in 12% of patients in the
  everolimus-treated group

Use in Specific Populations

• Because of the potential for serious adverse reactions in nursing
  infants, advise women to discontinue breastfeeding during treatment
• LENVIMA may result in reduced fertility in females of reproductive
  potential and may result in damage to male reproductive tissues,
  leading to reduced fertility of unknown duration

For more information about LENVIMA, click here
for the full Prescribing Information.

About KEYTRUDA

^®

(pembrolizumab) Injection
100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of
the body’s immune system to help detect and fight tumor cells. KEYTRUDA
is a humanized monoclonal antibody that blocks the interaction between
PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes
which may affect both tumor cells and healthy cells.

KEYTRUDA (pembrolizumab) Indications and Dosing in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a fixed dose of 200 mg every three weeks until
disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment
of patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as
determined by an FDA-approved test, with no EGFR or ALK genomic tumor
aberrations.

KEYTRUDA (pembrolizumab), as a single agent, is also indicated for the
treatment of patients with metastatic NSCLC whose tumors express PD-L1
(TPS ≥1%) as determined by an FDA-approved test, with disease
progression on or after platinum-containing chemotherapy. Patients with
EGFR or ALK genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated
for the first-line treatment of patients with metastatic nonsquamous
NSCLC. This indication is approved under accelerated approval based on
tumor response rate and progression-free survival. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg
every three weeks until disease progression, unacceptable toxicity, or
up to 24 months in patients without disease progression.

When administering KEYTRUDA (pembrolizumab) in combination with
chemotherapy, KEYTRUDA should be administered prior to chemotherapy when
given on the same day. See also the Prescribing Information for
pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic head and neck squamous cell carcinoma (HNSCC) with disease
progression on or after platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with refractory classical Hodgkin lymphoma (cHL), or who have relapsed
after three or more prior lines of therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. In adults with cHL, KEYTRUDA (pembrolizumab) is
administered at a fixed dose of 200 mg every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression. In pediatric patients with cHL, KEYTRUDA
(pembrolizumab) is administered at a dose of 2 mg/kg (up to a maximum of
200 mg) every three weeks until disease progression or unacceptable
toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible for
cisplatin-containing chemotherapy. This indication is approved under
accelerated approval based on tumor response rate and duration of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.

KEYTRUDA is also indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who have disease progression
during or following platinum-containing chemotherapy or within 12 months
of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with unresectable or metastatic microsatellite instability-high (MSI-H)
or mismatch repair deficient (dMMR)

• solid tumors that have progressed following prior treatment and who
  have no satisfactory alternative treatment options, or
• colorectal cancer that has progressed following treatment with
  fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. The safety and
effectiveness of KEYTRUDA in pediatric patients with MSI-H central
nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease progression. In
children with MSI-H cancer, KEYTRUDA (pembrolizumab) is administered at
a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent
locally advanced or metastatic gastric or gastroesophageal junction
(GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score
(CPS) ≥1] as determined by an FDA-approved test, with disease
progression on or after two or more prior lines of therapy including
fluoropyrimidine- and platinum-containing chemotherapy and if
appropriate, HER2/neu-targeted therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. The recommended dose of KEYTRUDA is 200 mg every
three weeks until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA

^®
 (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%)
pneumonitis, and occurred more frequently in patients with a history of
prior thoracic radiation (6.9%) compared to those without (2.9%).
Monitor patients for signs and symptoms of pneumonitis. Evaluate
suspected pneumonitis with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA
for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or
recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48
(1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3
(1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms
of colitis. Administer corticosteroids for Grade 2 or greater colitis.
Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for
Grade 4 colitis.

KEYTRUDA (pembrolizumab) can cause immune-mediated hepatitis. Hepatitis
occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for
changes in liver function. Administer corticosteroids for Grade 2 or
greater hepatitis and, based on severity of liver enzyme elevations,
withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of
2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%),
and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency).
Administer corticosteroids and hormone replacement as clinically
indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for
Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. The incidence of new or worsening hypothyroidism was
higher in patients with HNSCC, occurring in 28 (15%) of 192 patients
with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis
occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid
function (at the start of treatment, periodically during treatment, and
as indicated based on clinical evaluation) and for clinical signs and
symptoms of thyroid disorders. Administer replacement hormones for
hypothyroidism and manage hyperthyroidism with thionamides and
beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade
3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Administer insulin for type 1 diabetes, and withhold

KEYTRUDA (pembrolizumab) and administer antihyperglycemics in patients
with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9
(0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal
function. Administer corticosteroids for Grade 2 or greater nephritis.
Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for
Grade 3 or 4 nephritis.

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative
dermatitis, and bullous pemphigoid, can occur. Monitor patients for
suspected severe skin reactions and based on the severity of the adverse
reaction, withhold or permanently discontinue KEYTRUDA (pembrolizumab)
and administer corticosteroids. For signs or symptoms of SJS or TEN,
withhold KEYTRUDA and refer the patient for specialized care for
assessment and treatment. If SJS or TEN is confirmed, permanently
discontinue KEYTRUDA.

KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. These immune-mediated reactions may occur in any organ
system. For suspected immune-mediated adverse reactions, ensure adequate
evaluation to confirm etiology or exclude other causes. Based on the
severity of the adverse reaction, withhold KEYTRUDA and administer
corticosteroids. Upon improvement to Grade 1 or less, initiate
corticosteroid taper and continue to taper over at least 1 month. Based
on limited data from clinical studies in patients whose immune-related
adverse reactions could not be controlled with corticosteroid use,
administration of other systemic immunosuppressants can be considered.
Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less
following corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 2799 patients:
arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. In
addition, myelitis and myocarditis were reported in other clinical
trials, including classical Hodgkin lymphoma, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use
of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection
in solid organ transplant recipients. Consider the benefit of treatment
with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have been
reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and
symptoms of infusion-related reactions, including rigors, chills,
wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
KEYTRUDA.

Immune-mediated complications, including fatal events, occurred in
patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients
with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA
(pembrolizumab) on any trial, 6 patients (26%) developed
graft-versus-host disease (GVHD), one of which was fatal, and 2 patients
(9%) developed severe hepatic veno-occlusive disease (VOD) after
reduced-intensity conditioning, one of which was fatal. Cases of fatal
hyperacute GVHD after allogeneic HSCT have also been reported in
patients with lymphoma who received a PD-1 receptor–blocking antibody
before transplantation.

These complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients closely for early evidence
of transplant-related complications such as hyperacute GVHD, severe
(Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic
VOD, and other immune-mediated adverse reactions, and intervene promptly.

In clinical trials in patients with multiple myeloma, the addition of
KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in
increased mortality. Treatment of these patients with a PD-1 or PD-L1
blocking antibody in this combination is not recommended outside of
controlled clinical trials.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when
administered to a pregnant woman. If used during pregnancy, or if the
patient becomes pregnant during treatment, apprise the patient of the
potential hazard to a fetus. Advise females of reproductive potential to
use highly effective contraception during treatment and for 4 months
after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9%
of 555 patients with advanced melanoma; adverse reactions leading to
discontinuation in more than one patient were colitis (1.4%), autoimmune
hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
cardiac failure (0.4%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab
were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that occurred at
the same or lower rate than with KEYTRUDA.

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse
reactions in 8% of 682 patients with metastatic NSCLC. The most common
adverse event resulting in permanent discontinuation of KEYTRUDA was
pneumonitis (1.8%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 23% of patients; the most common (≥1%) were
diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation
(1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common
adverse reactions (occurring in at least 20% of patients and at a higher
incidence than with docetaxel) were decreased appetite (25% vs 23%),
dyspnea (23% vs 20%), and nausea (20% vs 18%).

In KEYNOTE-021(G1), when KEYTRUDA (pembrolizumab) was administered in
combination with carboplatin and pemetrexed (carbo/pem) in advanced
nonsquamous NSCLC, KEYTRUDA was discontinued in 10% of 59 patients. The
most common adverse reaction resulting in discontinuation of KEYTRUDA
(≥2%) was acute kidney injury (3.4%). Adverse reactions leading to
interruption of KEYTRUDA occurred in 39% of patients; the most common
(≥2%) were fatigue (8%), neutrophil count decreased (8%), anemia (5%),
dyspnea (3.4%), and pneumonitis (3.4%). The most common adverse
reactions (≥20%) with KEYTRUDA compared to carbo/pem alone were fatigue
(71% vs 50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42%
vs 21%), vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs
23%), decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24%
vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs
4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia
(20% vs 3.2%), upper respiratory tract infection (20% vs 3.2%), and
arthralgia (15% vs 24%). This study was not designed to demonstrate a
statistically significant difference in adverse reaction rates for
KEYTRUDA as compared to carbo/pem alone for any specified adverse
reaction.

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in
17% of 192 patients with HNSCC. Serious adverse reactions occurred in
45% of patients. The most frequent serious adverse reactions reported in
at least 2% of patients were pneumonia, dyspnea, confusional state,
vomiting, pleural effusion, and respiratory failure. The most common
adverse reactions (reported in at least 20% of patients) were fatigue,
decreased appetite, and dyspnea. Adverse reactions occurring in patients
with HNSCC were generally similar to those occurring in patients with
melanoma or NSCLC, with the exception of increased incidences of facial
edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening
hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5%
of 210 patients with cHL, and treatment was interrupted due to adverse
reactions in 26% of patients. Fifteen percent (15%) of patients had an
adverse reaction requiring systemic corticosteroid therapy. Serious
adverse reactions occurred in 16% of patients. The most frequent serious
adverse reactions (≥1%) included pneumonia, pneumonitis, pyrexia,
dyspnea, GVHD, and herpes zoster. Two patients died from causes other
than disease progression; one from GVHD after subsequent allogeneic HSCT
and one from septic shock. The most common adverse reactions (occurring
in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-052, KEYTRUDA (pembrolizumab) was discontinued due to adverse
reactions in 11% of 370 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reactions (in ≥20% of
patients) were fatigue (38%), musculoskeletal pain (24%), decreased
appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).
Eighteen patients (5%) died from causes other than disease progression.
Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis
which led to death, and 3 patients (0.8%) experienced pneumonia which
led to death. Adverse reactions leading to interruption of KEYTRUDA
occurred in 22% of patients; the most common (≥1%) were liver enzyme
increase, diarrhea, urinary tract infection, acute kidney injury,
fatigue, joint pain, and pneumonia. Serious adverse reactions occurred
in 42% of patients, the most frequent (≥2%) of which were urinary tract
infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8%
of 266 patients with locally advanced or metastatic urothelial
carcinoma. The most common adverse reaction resulting in permanent
discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions
leading to interruption of KEYTRUDA occurred in 20% of patients; the
most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%),
and colitis (1.1%). The most common adverse reactions (≥20%) in patients
who received KEYTRUDA vs those who received chemotherapy were fatigue
(38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%),
decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs
13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract infection,
pneumonia, anemia, and pneumonitis.

It is not known whether KEYTRUDA is excreted in human milk. Because many
drugs are excreted in human milk, instruct women to discontinue nursing
during treatment with KEYTRUDA and for 4 months after the final dose.

There is limited experience in pediatric patients. In a study, 40
pediatric patients (16 children aged 2 years to younger than 12 years
and 24 adolescents aged 12 years to 18 years) with advanced melanoma,
lymphoma, or PD-L1–positive advanced, relapsed, or refractory solid
tumors were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients
received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34
patients (85%) receiving KEYTRUDA for 2 doses or more. The safety
profile in these pediatric patients was similar to that seen in adults
treated with KEYTRUDA. Toxicities that occurred at a higher rate (≥15%
difference) in these patients when compared to adults under 65 years of
age were fatigue (45%), vomiting (38%), abdominal pain (28%),
hypertransaminasemia (28%), and hyponatremia (18%).

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

and Patient Information/Medication Guide for KEYTRUDA at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

Eisai’s Focus on Cancer

Eisai regards oncology as a key therapeutic area and is aiming to
discover revolutionary new medicines with the potential to cure cancer
by leveraging drug creation base technologies cultivated through the
discovery of Lenvima and Halaven, as well as technologies associated
with organic synthetic chemistry and drug discovery science. Eisai’s
research groups in Japan and the United States are working on drug
discovery activities using drug discovery platforms mainly for the
cancer microenvironment, driver gene mutation and aberrant splicing in
cancer cells, that are Eisai’s strengths.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based
pharmaceutical company headquartered in Japan. We define our corporate
mission as “giving first thought to patients and their families and to
increasing the benefits health care provides,” which we call our human
health care (hhc) philosophy. With approximately 10,000
employees working across our global network of R&D facilities,
manufacturing sites and marketing subsidiaries, we strive to realize our hhc
philosophy by delivering innovative products in various therapeutic
areas with high unmet medical needs, including Oncology and Neurology.

As a global pharmaceutical company, our mission extends to patients
around the world through our investment and participation in
partnership-based initiatives to improve access to medicines in
developing and emerging countries.

For more information about Eisai Co., Ltd., please visit www.eisai.com.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, helping people
fight cancer is our passion and supporting accessibility to our cancer
medicines is our commitment. Our focus is on pursuing research in
immuno-oncology and we are accelerating every step in the journey – from
lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program evaluating our anti-PD-1 therapy across more than 30
tumor types. We also continue to strengthen our immuno-oncology
portfolio through strategic acquisitions and are prioritizing the
development of several promising immunotherapeutic candidates with the
potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies and animal health products, we
work with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
visit www.merck.com

and connect with us on Twitter, Facebook, Instagram,
YouTube
and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’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; the company’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 the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’s 2017 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).

Eisai Public Relations Department
+81-(0)3-3817-5120
or
Eisai Investor Relations
+81-(0)3-3817-3016
or
Merck Relations
Pamela Eisele, 267-305-3558
or
Ann Bush, 908-740-6677
or
Merck Investor Relations
Teri Loxam, 908-740-1986
or
Peter Dannenbaum, 908-740-1037