SAN FRANCISCO, Nov. 20, 2014 /PRNewswire/ -- Nektar Therapeutics
(NASDAQ: NKTR) today announced results of a study investigating the
preclinical anti-tumor activity and tolerability of etirinotecan
pegol (NKTR-102) in combination with the PARP inhibitor rucaparib
in a BRCA1-deficient MX-1 breast tumor model. The preclinical study
results demonstrated that all dose combinations of NKTR-102 and
rucaparib were well-tolerated, synergistic, and led to 100%
prolonged survival in this tumor model. These data were presented
during the Symposium on Molecular Targets and Cancer Therapeutics
in Barcelona, Spain, sponsored by
the European Organisation for Research and Treatment of Cancer
(EORTC), the National Cancer Institute (NCI) and the American
Association for Cancer Research (AACR).
"We are encouraged by these results which demonstrate that
NKTR-102 in combination with the PARP inhibitor rucaparib has a
synergistic effect resulting in 100% prolonged survival in a BRCA
1-deficient tumor model," said Stephen K.
Doberstein, Ph.D., senior vice president and chief
scientific officer of Nektar Therapeutics. "As a next-generation
topo-I inhibitor with broad anti-tumor activity, NKTR-102 has the
potential to be combined with a number of targeted agents in
multiple tumor settings."
NKTR-102 is the first long-acting topoisomerase I inhibitor with
an extended half-life and a unique structure that is also designed
to concentrate the drug in tumors. In patients, NKTR-102 leads to
greatly prolonged plasma SN38 exposure compared to irinotecan
(elimination half-life of 50 days compared to 2 days) yet peak SN38
concentrations are at least 5- to 10-times less, which may also
result in a favorable tolerability profile.
Preclinical Study Design and Results
Study
investigators initiated tumor xenografts with MX-1 human breast
carcinomas maintained by serial subcutaneous transplantation in
female athymic nude (Crl:NU(Ncr)-Foxn1nu), 8-week-old mice. On the
day of tumor implant, each test mouse received a 1-mm3
MX-1 fragment implanted subcutaneously in the right flank. Animals
were randomized into treatment groups (n=10/grp) when their tumors
reached 63-196 mm3 and subsequently received either
vehicle, NKTR-102, rucaparab, or combinations of NKTR-102 +
rucaparib. Doses selected were known to provide clinically relevant
exposure levels. Twice weekly, animals were weighed, and tumor
volumes were measured until the endpoint (2000 mm3 or
Day 88) was met. Efficacy was measured by tumor growth delay and
regression response rate.
NKTR-102 and rucaparib in combination exhibited marked synergy,
demonstrated by durable complete responses, even at the lowest
doses of both agents dosed in combination. The combination of
NKTR-102 and rucaparib was tolerated at all dose levels. Doses used
in this study provide exposures of NKTR-102 (SN38 trough) and
rucaparib that are achievable clinically, underscoring the
translational relevance of these results.
Combination studies of NKTR-102 and rucaparib are ongoing in
patient-derived xenograft models in collaboration with Professor
Paul Haluska at Mayo Clinic and
Clovis Oncology.
About NKTR-102
NKTR-102 is currently being evaluated in a Phase 3, open-label,
randomized, multicenter study called the BEACON study. BEACON
enrolled 852 women with locally recurrent or metastatic breast
cancer, who have previously been treated with anthracycline, taxane
or capecitabine (ATC), and is being conducted at approximately 150
sites worldwide including North
America, Western Europe,
Russia and the Republic of Korea.
Nearly half of the patients enrolled in BEACON were located in
North America. Patients were
randomized on a 1:1 basis to receive 145 mg/m2 of single-agent
NKTR-102 once every three weeks or a single agent of physician's
choice. The physician's choice agents include: ixabepilone,
vinorelbine, gemcitabine, eribulin, or a taxane. Randomization was
stratified by geographic region, prior use of eribulin and receptor
status.
The primary endpoint of the BEACON study is overall survival;
secondary endpoints include progression-free survival, objective
tumor response rates, clinical benefit rate, duration of response,
pharmacokinetics, safety, quality-of-life measurements, and
pharmacoeconomic implications. The study is also evaluating
specific biomarker data to assess correlation with objective tumor
response rates, progression-free survival, overall survival and
selected toxicities.
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 MOVANTIKTM, 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 AstraZeneca agreement also includes NKTR-119, an earlier
stage development program that is a co-formulation of
MOVANTIKTM and an opioid. NKTR-181, a wholly-owned
mu-opioid analgesic molecule for chronic pain conditions, has
completed Phase 2 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 oncology, etirinotecan pegol (NKTR-102) is being
evaluated in a Phase 3 clinical study (the BEACON study) for the
treatment of metastatic breast cancer. In hemophilia, BAX 855, a
longer-acting PEGylated Factor VIII therapeutic is in Phase 3
development conducted by partner Baxter. 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 MOVANTIKTM, 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.
MOVANTIKTM is a trademark of the AstraZeneca group of
companies.
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 etirinotecan pegol
(NKTR-102) in combination with the PARP inhibitor rucaparib; 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) 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; (ii) 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;
(iii) acceptance, review and approval decisions for new drug
applications by health authorities is an uncertain and evolving
process and health authorities retain significant discretion at all
stages of the regulatory review and approval decision process; (iv)
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; (v) patents may not issue from our
patent applications for our drug candidates, patents that have
issued may not be enforceable, or additional intellectual property
licenses from third parties may be required; and (vi) 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 November 7, 2014. 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
SOURCE Nektar Therapeutics