SAN FRANCISCO, Oct. 7, 2015 /PRNewswire/ -- Nektar Therapeutics
(NASDAQ:NKTR) today announced that it has submitted an
Investigational New Drug (IND) application to the U.S. Food and
Drug Administration (FDA) for NKTR-214, its lead immuno-oncology
candidate. NKTR-214 is a CD122-biased immune-stimulatory cytokine
that is designed to stimulate the patient's own immune system to
destroy cancer cells. The company plans to initiate a Phase 1/2
clinical study by the end of 2015. The study will evaluate the
safety, tolerability and efficacy of NKTR-214 in patients with
solid tumor malignancies and will include expansion cohorts that
will evaluate NKTR-214 both as a single-agent and in combination
with a checkpoint inhibitor.
"As a new cytokine with biased receptor activity and an
antibody-like dosing schedule, NKTR-214 could emerge as a
differentiated immuno-oncology therapy that specifically stimulates
T-cell growth to fight cancer," said Stephen Doberstein, PhD, Senior Vice President
and Chief Scientific Officer of Nektar. "In preclinical studies
with NKTR-214, we not only observed single-agent efficacy in
multiple tumor models, but when administered in combination with a
checkpoint inhibitor, we see a dramatic immune-educating
vaccine-like effect with NKTR-214. We are excited to start our
first-in-human study and we expect to have initial data from the
dose-escalation phase of the trial by the second half of 2016."
The Phase 1/2 clinical program will be conducted at multiple
clinical sites including MD Anderson Cancer Center and Yale Cancer
Center. In addition to the Phase 1/2 clinical program, Nektar and
MD Anderson will conduct translational research to identify
predictive biomarkers that can be used in the future development of
NKTR-214.
About NKTR-214
NKTR-214 is a CD122-biased
immune-stimulatory cytokine that is designed to preferentially
stimulate the expansion and maintenance of CD8-positive effector T
cells, which are tumor-killing cells found naturally in the body.
CD122, which is also known as the Interleukin-2 (IL-2) receptor
beta subunit, is a key signaling receptor that is known to increase
the proliferation of CD8-positive effector T cells.1
These tumor-killing cells comprise a key component of the tumor
infiltrating lymphocytes that provide cell-mediated anti-tumor
effects.1 By biasing activation to the CD122 receptor,
NKTR-214 enhances the generation of CD8-positive T cells in the
tumor.
In preclinical studies, a single dose of NKTR-214 resulted in an
approximate 400-fold AUC exposure within the tumor compared with an
equivalent dose of aldesleukin, an existing IL-2 therapy. This
increase potentially enables, for the first time, an antibody-like
dosing regimen for a cytokine.2
At the Inaugural CRI-CIMT-EATI-AACR Immunotherapy Conference in
New York in September 2015, Nektar presented data
demonstrating that NKTR-214 induces durable and specific anti-tumor
immunity as a single agent and when combined with checkpoint
inhibitors in preclinical models. As a single agent, NKTR-214
demonstrated efficacy in multiple preclinical models. In
combination with either anti-CTLA4 or anti-PD-1 checkpoint
inhibitor therapies, NKTR-214 produced durable anti-tumor
immunotherapeutic effects, which persisted long after the
termination of dosing. In a preclinical tumor re-challenge study,
sequential dosing of anti-CTLA-4 followed by NKTR-214 resulted in
durable and complete responses. At 142 days following the final
dose, with no additional treatment, the complete responders
demonstrated sustained resistance to multiple tumor re-challenges.
In highly-resistant established melanoma tumor models, treatment
with NKTR-214 resulted in a controlled, sustained and biased T-cell
activating signal and a mean ratio of CD8-positive T cells to
CD4-positive regulatory T-cells (which can suppress tumor killing)
of 450:1 in the tumor infiltrating lymphocytes.
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. NKTR-171, a
wholly-owned new sodium channel blocker being developed as an oral
therapy for the treatment of peripheral neuropathic pain, is in
Phase 1 clinical development. In hemophilia, ADYNOVATE™
[Antihemophilic Factor (Recombinant)], a longer-acting PEGylated
Factor VIII therapeutic has been filed for approval in the U.S. by
partner Baxalta Inc. 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 nine approved products in the
U.S. or Europe through
partnerships with leading biopharmaceutical companies, including
AstraZeneca's MOVANTIK™, 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" within the meaning of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements 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
based on preclinical findings and the value and potential of our
technology and 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) the IND for NKTR-214 is currently under review by the FDA and
until the 30-day review period has elapsed, there is the
possibility that the start of the Phase 1 clinical study may be
delayed until any and all issues raised by the FDA have been
addressed in a satisfactory manner; (ii) positive preclinical
efficacy findings, such as those for NKTR-214 reported in this
press release, are subject to inherent scientific and medical
uncertainties typical for this early stage of drug development and
may not be confirmed in clinical trials; (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 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 commercial launch of drug candidates 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 the
application of our technology platform to potential new drug
candidates is therefore highly uncertain and unpredictable and one
or more research and development programs could fail; (vi) patents
may not issue from our patent applications for our drug candidates
including NKTR-214, patents that have issued may not be
enforceable, or additional intellectual property licenses from
third parties may be required; and (vii) the outcome of any
existing or future intellectual property or other litigation
related to our drug candidates and those of our collaboration
partners. Other important risks and uncertainties set forth in our
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission on August 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:
Investors
Jennifer Ruddock of Nektar
Therapeutics
415-482-5585
Media
Nadia Hasan of WCG
212-257-6738
1. Boyman, J., et al., Nature Reviews Immunology, 2012, 12,
180-190.
2. Hoch U, at al. AACR; Mol Cancer Ther. 2013;12(11 Suppl):Abstract
nr B296.
3. Data on file. Nektar Therapeutics
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/nektar-submits-investigational-new-drug-application-ind-for-nktr-214-to-treat-solid-tumor-malignancies-300155671.html
SOURCE Nektar Therapeutics