SAN FRANCISCO, June 6, 2016 /PRNewswire/ -- Nektar Therapeutics
(NASDAQ: NKTR) today announced new preclinical data for NKTR-214,
an immuno-stimulatory CD-122 biased cytokine currently being
evaluated in cancer patients with solid tumors in a Phase 1/2
clinical trial being conducted at MD Anderson Cancer Center and
Yale Cancer Center. The new preclinical data presented demonstrate
that treatment with single-agent NKTR-214 mobilizes tumor-killing T
cells into colon cancer tumors. In addition, mouse
pharmacodynamics data demonstrated that a single dose of NKTR-214
can increase and sustain STAT5 phosphorylation (a marker of IL-2
pathway activation) through one week post-dose. These data were
presented at the American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago, IL from
June 3-7, 2016.
"These latest data build upon our growing body of preclinical
evidence demonstrating the unique mechanism of NKTR-214," added
Jonathan Zalevsky, PhD, Vice
President, Biology and Preclinical Development at Nektar
Therapeutics. "The studies presented at ASCO show that NKTR-214
promotes tumor-killing immune cell accumulation directly in the
tumor, providing a mechanistic basis for its significant anti-tumor
activity in multiple preclinical tumor models. The ability to
grow TILs1 in vivo and replenish the immune system is
exceptionally important. We've now learned that many human tumors
lack sufficient TIL populations and the addition of the NKTR-214
TIL-enhancing MOA could improve the success of many checkpoint
inhibitors and other agents, and allow more patients to benefit
from immuno-therapy."
In studies previously published for NKTR-214, when mice bearing
established breast cancer tumors are treated with NKTR-214 and
anti-CTLA4 (a checkpoint inhibitor therapy known as ipilimumab for
human treatment), a large proportion of mice become tumor-free.
Anti-tumor immune memory was demonstrated when tumor-free mice were
re-challenged by implant with a new breast cancer tumor and then
found to clear the new tumor, without further therapy. The
new data presented at ASCO demonstrate that upon re-challenge,
there is a rapid expansion of newly proliferative CD8 T cells and
particularly CD8 effector memory T cells. Both cell populations
were readily detectable in multiple tissues (blood, spleen, and
lymph nodes) and likely contribute to the anti-tumor effect
observed in these animals. Adoptive transfer studies confirmed the
immune-memory effect as transplant of splenocytes from tumor-free
mice into naïve recipients provided the ability to resist tumor
growth.
"NKTR-214 provides a highly unique immune activation profile
that allows it to access the IL-2 pathway without pushing the
immune system into pathological overdrive," said Dr. Steve Doberstein, Senior Vice President and
Chief Scientific Officer. "NKTR-214's unique immune-stimulatory
profile and antibody-like dosing schedule positions it as a
potentially important medicine within the immuno-oncology
landscape."
The data presentation at ASCO entitled, "Immune memory in
nonclinical models after treatment with NKTR-214, an engineered
cytokine biased towards expansion of CD8+ T cells in tumor," can be
accessed
at http://www.nektar.com/2016_NKTR-214_ASCO_poster.pdf
NKTR-214 is a CD122-biased agonist designed to stimulate the
patient's own immune system to kill tumor cells by preferentially
activating production of specific immune cells which promote tumor
killing, including CD8-positive T cells and Natural Killer (NK)
cells, within the tumor micro-environment. CD122, which is
also known as the Interleukin-2 receptor beta subunit, is a key
signaling receptor that is known to increase proliferation of these
types of T cells.2
In preclinical studies, NKTR-214 demonstrated a highly favorable
mean ratio of 450:1 within the tumor micro-environment of
CD8-positive effector T cells relative to regulatory T
cells.3 Furthermore, the pro-drug design of
NKTR-214 enables an antibody-like dosing regimen for an
immuno-stimulatory cytokine.4
About the NKTR-214 Phase 1/2 Clinical Study
A Phase 1/2 clinical study is underway to evaluate NKTR-214 in
patients with advanced solid tumors, including melanoma, renal cell
carcinoma and non-small cell lung cancer. The first stage of
this study, which is expected to be complete in the second half of
2016, is evaluating escalating doses of 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 identify a recommended
Phase 2 dose. In addition, the study will also assess the
immunologic effect of NKTR-214 on TILs and other immune cells in
both blood and tumor tissue, and it will also include TCR
repertoire profiling. Dose expansion cohorts are planned to
evaluate NKTR-214 in specific tumor types, including melanoma,
renal cell carcinoma and non-small cell lung cancer.
The NKTR-214 clinical study is being conducted initially at two
primary investigator sites: MD Anderson Cancer
Center under Drs. Patrick Hwu and Adi Diab;
and Yale Cancer Center, under Drs. Mario
Sznol and Michael Hurwitz. Patients and physicians
interested in the ongoing NKTR-214 study can 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 Nektar
Nektar Therapeutics has a robust R&D pipeline and portfolio of
approved partnered medicines in oncology, pain, immunology and
other therapeutic areas. In the area of oncology, Nektar is
developing NKTR-214, an immuno-stimulatory CD122-biased agonist,
that is in Phase 1/2 clinical development for patients with solid
tumors. ONZEALD™ (etirinotecan pegol), a long-acting topoisomerase
I inhibitor, is being developed for patients with advanced breast
cancer and brain metastases and is partnered with Daiichi Sankyo in
Europe. 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. and Japan for
patients over 12 with hemophilia A. In anti-infectives, the company
has two collaborations with Bayer Healthcare, Cipro Inhale in Phase
3 for non-cystic fibrosis bronchiectasis and Amikacin Inhale in
Phase 3 for 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™, 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.
ONZEALD™ is a trademark of Nektar Therapeutics.
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; (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) certain other important
risks and uncertainties set forth in our Quarterly Report on Form
10-Q filed with the Securities and Exchange
Commission on May 4, 2016. 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:
Jennifer Ruddock of Nektar
Therapeutics
415-482-5585
Jodi Sievers of Nektar
Therapeutics
415-482-5593
For Media:
Dan Budwick of Pure Communications,
Inc.
(973) 271-6085
dan@purecommunicationsinc.com
- TILs (tumor infiltrating lymphocytes)
- Boyman, J., et al., Nature Reviews Immunology, 2012, 12,
180-190.
- Charych, D., et al., Cancer Res. 2013;73(8 Suppl):Abstract nr
482 and Data on file.
- Hoch U, at al. AACR; Mol Cancer Ther. 2013;12(11
Suppl):Abstract nr B296.
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