Early Findings Exploring the Relationship of PD-L1 Expression and Clinical Outcomes with MK-3475, Merck’s Investigational Anti

  Early Findings Exploring the Relationship of PD-L1 Expression and Clinical
  Outcomes with MK-3475, Merck’s Investigational Anti-PD-1 Immunotherapy,
  Presented at AACR Annual Meeting 2014

Exploratory Analyses in Advanced Melanoma and NSCLC Presented in Oral Session

       Dr. Roger Perlmutter to Present at AACR Opening Plenary Session

Business Wire

WHITEHOUSE STATION, N.J. -- April 6, 2014

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today
announced the presentation of early findings from studies exploring the
relationship between tumor PD-L1 expression and clinical outcomes following
monotherapy treatment with MK-3475, an investigational anti-PD-1
immunotherapy, in patients with advanced melanoma and advanced non-small cell
lung cancer (NSCLC). Responses were observed in patients with PD-L1 negative
tumors; although the preliminary findings for both tumor types suggest that
higher PD-L1 expression was associated with higher overall response rates.
Further study of the relationship between PD-L1 expression and responses to
MK-3475 as monotherapy and in combination with other treatments for melanoma,
NSCLC and other tumors is ongoing or planned.

These findings will be presented today in an oral session at the AACR Annual
Meeting 2014 in San Diego and were highlighted within the official AACR press
program. Separately, as part of today’s opening plenary session, Dr. Roger M.
Perlmutter, president, Merck Research Laboratories, will deliver a plenary
lecture entitled “Tumor-Specific Immune Activation: Immuno-Oncology Comes of
Age”.

“These exploratory analyses are providing us with insightful information
regarding the association of PD-L1 expression and clinical outcomes with
MK-3475,” said Dr. Eric Rubin, vice president, Oncology, Merck Research
Laboratories. “In both types of advanced cancers studied, we are seeing
durable responses in a wide range of patients, including those with PD-L1
negative tumors. We will continue to explore PD-L1 expression and other
selection markers across tumors in our MK-3475 development program.”

Preliminary PD-L1 Expression Analysis in Advanced Melanoma

Preliminary findings on PD-L1 expression in 125 evaluable advanced melanoma
patients, based on a minimum of 6-month follow-up from the ongoing Phase 1B
KEYNOTE-001 study, were presented by Dr. Adil Daud, co-director of the
University of California, San Francisco (UCSF) Melanoma Center, and director
of melanoma clinical research at the UCSF Helen Diller Family Comprehensive
Cancer Center, (abstract #5013). Results from the preliminary analysis showed
that 71 percent (n=89) of advanced melanoma patients had positive PD-L1 tumors
at the optimally defined cut-point of ≥1 percent of tumor cells stained, as
measured by immunohistochemistry (IHC). An additional cut-point of ≥10 percent
of cells stained by IHC measurement was also evaluated.

In the overall evaluable advanced melanoma population, the overall response
rate was 40 percent (n=113) as measured by RECIST 1.1 (Response Evaluation
Criteria in Solid Tumors). Based on the ≥1 percent cut-point, responses were
observed in 49 percent [95% CI; range 38-61] (n=83) (per RECIST criteria) of
patients with positive PD-L1 tumors and 13 percent [95% CI; range 4-31] (n=30)
of patients with PD-L1 negative tumors. When the ≥10 percent cut-point was
used, responses were observed in 52 percent [95% CI; range 40-65] (n=65) of
patients with PD-L1 positive tumors and 23 percent [95% CI; range 12-37]
(n=48) of patients with PD-L1 negative tumors.

The high prevalence of PD-L1 expression, along with the responses observed in
the overall population and patients with PD-L1 positive tumors based on the ≥1
percent cut-point, suggest that selecting patients for MK-3475 therapy based
on measurement of PD-L1 is of limited utility in this tumor. Preliminary
findings for overall disease control rates, median estimated progression-free
survival (PFS), and median estimated overall survival (OS) were also
presented.

Preliminary PD-L1 Expression Analysis in Advanced NSCLC

Preliminary findings on PD-L1 expression in 129 evaluable previously-treated
patients with advanced NSCLC, based on a minimum of 19-week follow-up from the
ongoing KEYNOTE-001 study, were presented by Dr. Leena Gandhi, assistant
professor of medicine at Harvard Medical School and thoracic oncologist at
Dana-Farber Cancer Institute (abstract #5014). Results from the preliminary
analysis showed that approximately 45 percent of advanced NSCLC patients had
positive PD-L1 tumors at a cut-point of ≥1 percent of tumor cells stained as
defined by IHC assessment. Based on this data set, the preliminary analysis
suggests that the optimal cut-point is ≥50 percent of tumor cells stained by
IHC assessment. When using this measurement, approximately 25 percent of
advanced NSCLC patients had tumors that strongly expressed PD-L1.

In the overall evaluable advanced NSCLC population, the overall response rate
was 19 percent (n=129) (per RECIST criteria). In evaluable PD-L1-positive
strong expresser population, responses were seen in 37 percent [95% CI; range
22-53] (n=15/41) (per RECIST criteria) of these patients, with responses also
observed in 11 percent [95% CI; range 6-20] (n=10/88) of patients with PD-L1
low or negative tumors. When the ≥1 percent cut-point was used, responses were
observed in 25 percent [95% CI; range 17-36] (n=22/87) of evaluable patients
with PD-L1 positive tumors and 7 percent [95% CI; range 2-20] (n=3/42) of
patients with PD-L1 negative tumors. Preliminary data on estimated median PFS
and estimated median OS were also presented.

No adverse events were presented as part of these exploratory analyses and
were consistent with those previously reported for MK-3475.

Additional Merck Oncology Data Presentations at AACR 2014

Additional Merck research presented at AACR include the following abstracts
(presented as posters on Wednesday, April 9):

  *mDX400, the murine analog against MK-3475 is active in immunocompetent,
    autochthonous murine models of melanoma and breast cancer (Abstract #5024)
  *Dissecting the dynamics of anti-PD1 immunotherapy in preclinical tumor
    models (Abstract #5025)

About MK-3475

Many tumors are able to evade the immune system through a mechanism that
exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an
investigational, highly selective anti-PD-1 immunotherapy designed to restore
the ability of the immune system to recognize and target cancer cells by
selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1
protein. By blocking PD-1, MK-3475 enables activation of the immune system’s
T-cells that target cancer, essentially by releasing a brake on the immune
system.

MK-3475 is being studied in 15 clinical trials estimated to enroll more than
4,000 patients across more than 30 types of cancer. Additional trials, both as
monotherapy and in combination with other cancer therapies, are planned. For
information on ongoing MK-3475 clinical trials please visit
http://www.merck.com/clinical-trials .

Merck announced Breakthrough Therapy designation for MK-3475 in advanced
melanoma by the U.S. Food and Drug Administration in April 2013. Merck
announced in January the initiation of a rolling submission of a Biologics
License Application for MK-3475 in advanced melanoma in the U.S. The company
expects to complete the submission in the first half of 2014.

About Advanced Melanoma

There were an estimated 232,000 new cases of melanoma diagnosed in 2012
worldwide. Melanoma is the most dangerous type of skin cancer and is the
leading cause of death from skin disease. While it accounts for only five
percent of all cases, melanoma is the cause of the vast majority of skin
cancer deaths. According to the American Cancer Society, an estimated 9,480
people in the U.S. died from advanced melanoma in 2013.

About Lung Cancer

Lung cancer is the leading cause of cancer death worldwide in both men and
women, with an estimated 1.5 million deaths worldwide each year, according to
the American Cancer Society. NSCLC is the most common type of lung cancer
representing about 85 percent of all lung cancer diagnoses.

About Merck

Today's Merck is a global healthcare leader working to help the world be well.
Merck is known as MSD outside the United States and Canada. Through our
prescription medicines, vaccines, biologic therapies, and consumer care 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 healthcare through far-reaching policies,
programs and partnerships. For more information, visit www.merck.com and
connect with us on Twitter, Facebook and YouTube.

Merck Forward-Looking Statement

This news release 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 healthcare legislation in the United States and
internationally; global trends toward healthcare 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).

Contact:

Media:
Ian McConnell, 973-901-5722
Claire Mulhearn, 908-423-7425
or
Investors:
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Justin Holko, 908-423-5088
 
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