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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