SAN FRANCISCO, Feb. 1, 2016 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced the publication in
Clinical Cancer Research of pre-clinical findings for
NKTR-214. The paper, titled "NKTR-214, an Engineered Cytokine
with Biased IL2 Receptor Binding, Increased Tumor Exposure, and
Marked Efficacy in Mouse Tumor Models," (Charych et al.,
Clin Cancer Res,
doi:10.1158/1078-0432.CCR-15-1631) documents a broad set of
pre-clinical data supporting the clinical advancement of
NKTR-214. Among the findings reported, treatment with
NKTR-214 led to durable and specific anti-tumor immunity in
multiple syngeneic mouse models both as a single agent and as
combination therapy with checkpoint inhibitors. In addition,
treatment with single-agent NKTR-214 in tumor-bearing mice resulted
in a controlled, sustained, and biased T-cell activation leading to
a 450:1 mean ratio of CD8-positive effector T cells to T-regulatory
cells in the tumor microenvironment, while maintaining more
balanced ratios in non-tumor tissues and circulation.
"NKTR-214 allows us to capture and harness the power of the IL-2
biological pathway, which is known to promote T cell growth, to
stimulate the body's own immune system to target and fight cancer.
The design of NKTR-214 gives it a combination of biophysical,
biochemical, and pharmacological properties that translate into a
desirable anti-tumor immune profile," said Stephen Doberstein, Ph.D., Senior Vice President
and Chief Scientific Officer of Nektar Therapeutics.
The newly published data documented in the paper also support
the favorable safety profile of NKTR-214. The compound was
well-tolerated in rodents and in non-human primates (NHPs).
Importantly, these pre-clinical safety studies showed that NKTR-214
did not lead to hypotension or vascular leak syndrome at predicted
clinical therapeutic doses.
As documented in the new publication, in a pre-clinical tumor
re-challenge study in an EMT6 mouse breast cancer model, dosing of
NKTR-214 in combination with anti-CTLA-4 antibody resulted in
durable and complete responses lasting up to 170 days (5.5
months). When tumor-free animals were re-challenged with the
same tumors with no additional treatment, the complete responders
demonstrated sustained vaccine-like resistance. These results
suggest that NKTR-214 provides a complementary mechanism of immune
activation when used concurrently with approved antibody
therapies.
"We are pleased that the unique mechanism, efficacy and safety
of NKTR-214 are now described and published in a prestigious
peer-reviewed journal that is widely read by oncologists,
scientists and physician-scientists," said Dr. Doberstein.
"We are continuing to advance NKTR-214 in an ongoing Phase 1/2
clinical trial in cancer patients and we expect to have preliminary
top-line results from the first stage of this study in the second
half of 2016."
About the NKTR-214 Phase 1/2 Clinical Study
NKTR-214 is currently being evaluated in a Phase 1/2 clinical
study in patients with advanced solid tumors, including melanoma,
renal cell carcinoma and non-small cell lung cancer. The
ongoing study is being conducted at MD Anderson Cancer Center and
Yale Cancer Center and is comprised of two stages. The first stage
is an open-label, multi-dose, dose-escalation study evaluating
single-agent NKTR-214 treatment in approximately 20 patients with
solid tumors. The primary objective of the first stage of the
study is to evaluate the safety and efficacy of NKTR-214, and to
define the recommended Phase 2 dose. In addition, the study
will assess preliminary anti-tumor activity, including objective
response rate (ORR). The immunologic effect of NKTR-214 on
tumor-infiltrating lymphocytes (TILs) and other immune cells in
both blood and tumor tissue will also be assessed. Following
the dose-escalation stage of the study, dose expansion cohorts are
planned to evaluate NKTR-214 in specific tumor types, including
melanoma, renal cell carcinoma and non-small cell lung cancer.
For more information on the ongoing NKTR-214 Study, please visit
the "Clinical Trials" section of www.mdanderson.org using
identifier 2015-0573 or visit
https://medicine.yale.edu/cancer/research/trials/active/858.trial.
About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine, which is
designed to stimulate the patient's own immune system to kill tumor
cells. By biasing activation to the CD122 receptor, NKTR-214
enhances CD8+ effector T cells (tumor-killing cells) in the tumor.
In pre-clinical studies, a single dose of NKTR-214 resulted in a
400-fold AUC exposure within the tumor compared with an equivalent
dose of the existing IL-2 therapy, enabling, for the first time, an
antibody-like dosing regimen for a cytokine.
About Nektar
Nektar Therapeutics has a robust R&D pipeline in pain,
oncology, hemophilia and other therapeutic areas. In the area of
pain, Nektar has an exclusive worldwide license agreement with
AstraZeneca for MOVANTIK™ (naloxegol), the first FDA-approved
once-daily oral peripherally-acting mu-opioid receptor antagonist
(PAMORA) medication for the treatment of opioid-induced
constipation (OIC), in adult patients with chronic, non-cancer
pain. The product is also approved in the European Union as
MOVENTIG® (naloxegol) and is indicated for adult patients with OIC
who have had an inadequate response to laxatives. The AstraZeneca
agreement also includes NKTR-119, an earlier stage development
program that is a co-formulation of MOVANTIK and an opioid.
NKTR-181, a wholly-owned mu-opioid analgesic molecule for chronic
pain conditions, is in Phase 3 development. In hemophilia, Nektar
has a collaboration agreement with Baxalta for ADYNOVATE™
[Antihemophilic Factor (Recombinant)], a longer-acting PEGylated
Factor VIII therapeutic approved in the U.S. in patients over 12
with hemophilia A. In anti-infectives, Amikacin Inhale is in Phase
3 studies conducted by Bayer Healthcare as an adjunctive treatment
for intubated and mechanically ventilated patients with
Gram-negative pneumonia.
Nektar's technology has enabled ten approved products in the
U.S. or Europe through
partnerships with leading biopharmaceutical companies, including
AstraZeneca's MOVANTIK™, Baxalta's ADYNOVATE™, UCB's Cimzia® for
Crohn's disease and rheumatoid arthritis, Roche's PEGASYS® for
hepatitis C and Amgen's Neulasta® for neutropenia.
Nektar is headquartered in San
Francisco, California, with additional operations in
Huntsville, Alabama and
Hyderabad, India. Further
information about the company and its drug development programs and
capabilities may be found online at http://www.nektar.com.
MOVANTIK™ is a trademark and MOVENTIG® is a registered trademark
of the AstraZeneca group of companies.
ADYNOVATE™ is a trademark of Baxalta Inc
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements which can
be identified by words such as: "anticipate," "intend," "plan,"
"expect," "believe," "should," "may," "will" and similar references
to future periods. Examples of forward-looking statements include,
among others, statements we make regarding the therapeutic
potential of NKTR-214, the timing of availability of clinical data
for NKTR-214, and the potential of our technology and drug
candidates in our research and development pipeline.
Forward-looking statements are neither historical facts nor
assurances of future performance. Instead, they are based only on
our current beliefs, expectations and assumptions regarding the
future of our business, future plans and strategies, anticipated
events and trends, the economy and other future conditions. Because
forward-looking statements relate to the future, they are subject
to inherent uncertainties, risks and changes in circumstances that
are difficult to predict and many of which are outside of our
control. Our actual results may differ materially from those
indicated in the forward-looking statements. Therefore, you should
not rely on any of these forward-looking statements. Important
factors that could cause our actual results to differ materially
from those indicated in the forward-looking statements include,
among others: (i) our statements regarding the therapeutic
potential of NKTR-214 are based on preclinical findings and
observations, (ii) NKTR-214 is in early-stage clinical development
and there are substantial risks that can unexpectedly occur for
numerous reasons including negative safety and efficacy findings in
the ongoing Phase 1 clinical study notwithstanding positive
findings in preclinical studies; (iii) our drug candidates and
those of our collaboration partners are in various stages of
clinical development and the risk of failure is high and can
unexpectedly occur at any stage prior to regulatory approval for
numerous reasons including negative safety and efficacy findings
even after positive findings in previous preclinical and clinical
studies; (iv) the timing of the commencement or end of clinical
trials and the availability of clinical may be delayed or
unsuccessful due to regulatory delays, slower than anticipated
patient enrollment, manufacturing challenges, changing standards of
care, evolving regulatory requirements, clinical trial design,
clinical outcomes, competitive factors, or delay or failure in
ultimately obtaining regulatory approval in one or more important
markets; (v) scientific discovery of new medical breakthroughs is
an inherently uncertain process and the future success of applying
our technology platform to potential new drug candidates (such as
NKTR-214) is therefore highly uncertain and unpredictable and one
or more research and development programs could fail; and (vi)
certain other important risks and uncertainties set forth in our
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission on November 6, 2015. Any
forward-looking statement made by us in this press release is based
only on information currently available to us and speaks only as of
the date on which it is made. We undertake no obligation to update
any forward-looking statement, whether written or oral, that may be
made from time to time, whether as a result of new information,
future developments or otherwise.
Contact:
For Investors and Media:
Jennifer Ruddock of Nektar
Therapeutics
415-482-5585
Jodi Sievers of Nektar
Therapeutics
415-482-5593
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