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
CONTACT: Merck Media Relations:
Pamela Eisele: (267) 305-3558
Claire Mulhearn: (908) 236-1118
Merck Investor Relations:
Justin Holko: (908) 740-1879
TetraLogic Investor Relations:
Pete A. Meyers: (610) 889-9900, x103
pete.meyers@tlog.com
TetraLogic Pharmaceuticals (CE) (USOTC:TLOG)
Historical Stock Chart
From Aug 2024 to Sep 2024
TetraLogic Pharmaceuticals (CE) (USOTC:TLOG)
Historical Stock Chart
From Sep 2023 to Sep 2024