TetraLogic and Merck to Collaborate on the Evaluation of Birinapant in Combination with KEYTRUDA® (pembrolizumab) in Solid Tumors

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April 20, 2015 7:00 am ET

MALVERN, Pa. & KENILWORTH, N.J.–(BUSINESS WIRE)–TetraLogic Pharmaceuticals Corporation (Nasdaq: TLOG), a clinical-stage
biopharmaceutical company focused on discovering and developing novel
small molecule therapeutics in oncology and infectious diseases, and
Merck (NYSE:MRK), known as MSD outside the United States and Canada,
announced today they have entered into an oncology clinical study
collaboration. The companies will collaborate on a Phase 1 study to
evaluate the safety and efficacy of birinapant, TetraLogic’s
SMAC-mimetic, in combination with KEYTRUDA® (pembrolizumab), Merck’s
anti-PD-1 therapy, in patients with relapsed or refractory solid tumors.
The study is expected to begin in late 2015.

KEYTRUDA and birinapant target different elements of cancer’s block
against the immune system. TetraLogic’s birinapant (TL32711) is a
potent, bivalent SMAC-mimetic that binds with differential affinity to
multiple members of the IAP family in order to re-establish the immune
system’s ability to kill abnormal cells via an extracellular TNF signal.
Merck’s KEYTRUDA is a humanized monoclonal antibody that blocks the
interaction between PD-1 (programmed death receptor-1) and its ligands,
PD-L1 and PD-L2. The proposed collaboration is based on preclinical data
that suggest SMAC-mimetics have the potential to enhance existing
immuno-oncology agents, such as KEYTRUDA.

“We are very excited to work with Merck to evaluate birinapant in
combination with KEYTRUDA,” said J. Kevin Buchi, President and Chief
Executive Officer of TetraLogic. “Both molecules are designed to help
the body’s immune system better attack cancer cells, and we think the
combination could be very promising.”

“We are establishing a broad base of clinical evidence with our
anti-PD-1 therapy, KEYTRUDA, as monotherapy across different types of
cancer,” said Dr. Eric Rubin, vice president and therapeutic area head,
oncology early-stage development, Merck Research Laboratories. “We
believe there is great potential to advance our clinical program and the
field of immuno-oncology research through strategic collaborations and
synergistic combinations, such as with KEYTRUDA and birinapant.”

Under the terms of the agreement, TetraLogic and Merck, through
subsidiaries, will collaborate on an initial Phase 1
dose-escalation study of birinapant in combination with KEYTRUDA in
patients with relapsed or refractory solid tumors. TetraLogic will
sponsor and fund the study and Merck will provide KEYTRUDA. The
companies have formed a Joint Development Committee to collaboratively
oversee the conduct of the study. Results from the study will be used to
determine the path for further clinical development of the combination.

About Birinapant

Cancer and chronically infected cells are able to evade a critical
mechanism by which the immune system normally kills abnormal or
genetically modified cells. They do this by upregulating the Inhibitors
of Apoptosis (IAP) Proteins. Birinapant (TL32711) is a potent, bivalent
SMAC-mimetic that binds with differential affinity to multiple members
of the IAP family in order to re-establish the immune system’s ability
to kill abnormal cells via an extracellular TNF signal. Birinapant has
been studied in over 350 patients, and is currently in Phase 1 and Phase
2 trials for Myelodysplastic Syndrome (MDS), Ovarian Cancer and
Hepatitis B.

About KEYTRUDA® (pembrolizumab)

KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks
the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By
binding to the PD-1 receptor and blocking the interaction with the
receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition
of the immune response, including the anti-tumor immune response.

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg
administered as an intravenous infusion over 30 minutes every three
weeks for the treatment of patients with unresectable or metastatic
melanoma and disease progression following ipilimumab and, if BRAF V600
mutation positive, a BRAF inhibitor. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. An improvement in survival or disease-related symptoms has not
yet been established. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in the
confirmatory trials.

Merck is advancing a broad and fast-growing clinical development program
for KEYTRUDA with more than 85 clinical trials – across more than 30
tumor types and over 14,000 patients – both as a monotherapy and in
combination with other therapies.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced melanoma
receiving KEYTRUDA (the approved indication in the United States),
including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients,
respectively. 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
pneumonitis.

Colitis (including microscopic colitis) occurred in 4 (1%) of 411
patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients
respectively, receiving KEYTRUDA. 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.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411
patients, including a Grade 4 case in 1 (0.2%) patient, receiving
KEYTRUDA. 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.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2
case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving
KEYTRUDA. Monitor for signs and symptoms of hypophysitis. Administer
corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA
for Grade 2; withhold or discontinue for Grade 3; and permanently
discontinue KEYTRUDA for Grade 4 hypophysitis.

Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, consisting
of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of
interstitial nephritis with renal failure (0.5%), one Grade 3 and one
Grade 4. 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.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2
or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively, receiving
KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients,
including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA.
Thyroid disorders can occur at any time during treatment. 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 corticosteroids for Grade 3 or greater hyperthyroidism.
Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for
Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with
replacement therapy without treatment interruption and without
corticosteroids.

Other clinically important immune-mediated adverse reactions can occur.
The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of patients treated with KEYTRUDA: exfoliative
dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic
anemia, partial seizures arising in a patient with inflammatory foci in
brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic
neuritis, and rhabdomyolysis.

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 of the adverse reaction to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or
less. Permanently discontinue KEYTRUDA for any severe or Grade 3
immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.

Based on its mechanism of action, KEYTRUDA may 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.

For the treatment of advanced melanoma, KEYTRUDA was discontinued for
adverse reactions in 6% of 89 patients who received the recommended dose
of 2 mg/kg and 9% of 411 patients across all doses studied. Serious
adverse reactions occurred in 36% of patients receiving KEYTRUDA. The
most frequent serious adverse drug reactions reported in 2% or more of
patients were renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in ≥20% of patients) were
fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%),
decreased appetite (26%), constipation (21%), arthralgia (20%), and
diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression or unacceptable toxicity. No formal pharmacokinetic drug
interaction studies have been conducted with KEYTRUDA. 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. Safety and effectiveness of KEYTRUDA have not
been established in pediatric patients.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck Oncology,
helping people fight cancer is our passion, supporting accessibility to
our cancer medicines is our commitment, and pursuing research in
immuno-oncology is our focus to potentially bring new hope to people
with cancer. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.

About Merck

Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside of the United States and Canada.
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 healthcare through
far-reaching policies, programs and partnerships. For more information,
visit www.merck.com
and connect with us on Twitter,
Facebook
and YouTube.

About TetraLogic Pharmaceuticals Corporation

TetraLogic is a clinical-stage biopharmaceutical company focused on
discovering and developing novel small molecule therapeutics in oncology
and infectious diseases. TetraLogic has two clinical-stage product
candidates in development: birinapant and SHAPE. Birinapant is currently
being tested in Phase 1 and Phase 2 clinical trials for hematological
malignancies and solid tumors, and is also being tested in a Phase 1b/2a
clinical trial in hepatitis B. SHAPE is currently being tested in a
Phase 2 clinical trial for early-stage cutaneous T-cell lymphoma.

TetraLogic Forward Looking Statement

Some of the statements in this release are forward looking statements
within the meaning of Section 27A of the Securities Act of 1933, Section
21E of the Securities Exchange Act of 1934 and the Private Securities
Litigation Reform Act of 1995, which involve risks and uncertainties.
These statements relate to future events or TetraLogic’s pre-clinical
and clinical development of birinapant, SHAPE and other clinical
programs, future expectations, plans and prospects. Although TetraLogic
believes that the expectations reflected in such forward-looking
statements are reasonable as of the date made, expectations may prove to
have been materially different from the results expressed or implied by
such forward-looking statements. TetraLogic has attempted to identify
forward looking statements by terminology including ‘‘believes,’’
‘‘estimates,’’ ‘‘anticipates,’’ ‘‘expects,’’ ‘‘plans,’’ ‘‘projects,’’
‘‘intends,’’ ‘‘potential,’’ ‘‘may,’’ ‘‘could,’’ ‘‘might,’’ ‘‘will,’’
‘‘should,’’ ‘‘approximately’’ or other words that convey uncertainty of
future events or outcomes to identify these forward-looking statements.
These statements are only predictions and involve known and unknown
risks, uncertainties, and other factors, including those discussed under
the heading “Risk Factors” in our Annual Report on Form 10-K filed with
the U.S. Securities and Exchange Commission (SEC) on February 26, 2015.
Any forward-looking statements contained in this release speak only as
of its date. We undertake no obligation to update any forward-looking
statements contained in this release to reflect events or circumstances
occurring after its date or to reflect the occurrence of unanticipated
events.

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 2014 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).

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

Merck Media Relations:
Pamela Eisele, 267-305-3558
or
Claire Mulhearn, 908-236-1118
or
Merck Investor Relations:
Justin Holko, 908-740-1879
or
TetraLogic Investor Relations:
Pete A. Meyers, 610-889-9900, x103
pete.meyers@tlog.com

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