Merck and DNAtrix Announce Phase 2 Immuno-Oncology Collaboration in Patients with Aggressive Form of Brain Cancer

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October 1, 2015 7:00 am ET

KENILWORTH, N.J. & HOUSTON–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, and
DNAtrix today announced they have entered into an oncology clinical
study collaboration to evaluate the efficacy and safety of DNX-2401,
DNAtrix’s oncolytic immunotherapy, in combination with KEYTRUDA®
(pembrolizumab), Merck’s anti-PD-1 therapy, in a Phase 2, multi-centered
study of patients with recurrent glioblastoma, the most aggressive form
of brain cancer for which there is no cure.

DNX-2401 is a conditionally replicative oncolytic adenovirus designed to
specifically target cells defective in the Retinoblastoma (Rb) pathway,
which is present in many cancers. Several DNX-2401 clinical studies have
demonstrated a favorable safety profile and strong tumor-killing
potential in patients with recurrent glioblastoma. 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. KEYTRUDA
is currently approved in the United States for certain types of advanced
metastatic melanoma.

“We are excited to enter into this important collaboration with Merck as
we investigate the potential anti-tumor effect that combining our two
immunotherapies – DNX-2401 and KEYTRUDA – may offer patients with this
aggressive disease,” said Frank Tufaro, Ph.D., chief executive officer
of DNAtrix.

“The collaboration with DNAtrix further strengthens our efforts to
progress the field of immuno-oncology and identify potential
combinations that will significantly advance the care of people with
cancers for which there have been few advancements,” said Dr. Eric
Rubin, vice president and therapeutic area head, oncology early-stage
development, Merck Research Laboratories. “We look forward to studying
the potential synergistic effects that combining DNX-2401 and KEYTRUDA
could have in the treatment of patients with recurrent glioblastoma.”

The agreement is between DNAtrix and Merck, through a subsidiary.
Additional details of the collaboration were not disclosed.

About Glioblastoma

Glioblastoma is a type of glioma, which are tumors that arise from glial
cells, or supportive brain cells that help to keep neurons in place and
functioning well. Glioblastoma is highly malignant because the cells
reproduce quickly and are supported by a large network of blood vessels.
While glioblastoma rarely spreads elsewhere in the body, these tumors
arise from normal brain cells, so it is easy for them to invade and live
within normal brain tissue. Glioblastoma represents 17
percent of all primary brain tumors and 54 percent of all gliomas.

About DNX-2401

DNX-2401 is an investigational oncolytic immunotherapy designed to treat
high grade gliomas. Upon tumor injection, DNX-2401 sets off a chain
reaction of tumor cell killing by selectively replicating within glioma
cells (but not normal cells), causing tumor destruction and further
spread of the oncolytic virus to adjacent tumor cells. This process can
also trigger an anti-tumor immune response. DNX-2401 is currently being
investigated in several clinical studies and has been well tolerated in
all settings. Compelling results from Phase I clinical studies in
recurrent glioblastoma indicate that DNX-2401 can (1) replicate in human
brain tumors for a period of weeks to months (2) trigger immune cell
infiltration into the tumor (3) cause ongoing tumor destruction
detectable by MRI and (4) induce durable responses to therapy. In these
studies, patient survival has been prolonged in a subset of patients,
including in those achieving a complete response.

About KEYTRUDA® (pembrolizumab)

KEYTRUDA 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 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.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or
3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving
KEYTRUDA. 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 patients for signs and symptoms of hypophysitis
(including hypopituitarism and adrenal insufficiency). 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.

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.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred
in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and
other signs and symptoms of diabetes. Administer insulin for type 1
diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia until
metabolic control is achieved.

Nephritis occurred in 3 (0.7%) patients, 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.

Other clinically important immune-mediated adverse reactions can occur.
The following clinically significant immune-mediated adverse reactions
occurred in patients treated with KEYTRUDA: exfoliative dermatitis,
uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial
seizures arising in a patient with inflammatory foci in brain
parenchyma, severe dermatitis including bullous pemphigoid, 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.

Infusion-related reactions, including severe and life-threatening
reactions, have occurred in patients receiving KEYTRUDA. Monitor
patients for signs and symptoms of infusion-related reactions including
rigors, chills, wheezing, pruritus, flushing, rash, hypotension,
hypoxemia, and fever. For severe or life-threatening reactions, stop
infusion and permanently discontinue KEYTRUDA.

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.

KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients.
Adverse reactions, reported in at least two patients, that led to
discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain.
Serious adverse reactions occurred in 36% of patients. The most frequent
serious adverse reactions, reported in 2% or more of patients, were
renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in at least 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.

About DNAtrix

DNAtrix is a privately held, clinical stage, biotechnology company
developing virus-driven immunotherapies for cancer. DNAtrix’s lead
product, DNX-2401, is a conditionally replicative oncolytic virus being
studied in clinical trials for recurrent glioblastoma, an incurable
brain cancer. The company is backed by Morningside Ventures and Mercury
Fund, and has been awarded a grant from the Cancer Prevention and
Research Institute of Texas (CPRIT). For more information, please visit
the company website at http://www.dnatrix.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 Oncology,
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. 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
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Forward-Looking Statement of Merck & Co., Inc., Kenilworth, NJ, USA

This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the
“company”) 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 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 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; 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 s
patents and other protections for innovative products; and the exposure
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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 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
An Phan, 908-255-6325
Investor Relations:
Teri Loxam, 908-740-1986
Justin Holko, 908-740-1879
or
DNAtrix
Investor/Media Relations:
Imran Alibhai, Ph.D.
ialibhai@dnatrix.com

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