SAN FRANCISCO, May 20, 2021 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced the publication of
preclinical data in the Journal of Translational
Autoimmunity describing NKTR-358, a first-in-class, composition
of stable PEG conjugates of native IL-2 designed to selectively
stimulate T regulatory (Treg) cell function. NKTR-358 is currently
in development for the treatment of a range of autoimmune and
inflammatory disorders. These published data demonstrate that
NKTR-358 has the ability to elicit sustained and preferential
proliferation and activation of Tregs in vivo without
corresponding increases in T effector cells.
"The publication in the Journal of Translational
Autoimmunity demonstrates, by a variety of measures, and across
species, that NKTR-358 induces sustained, selective proliferation
and activation of regulatory T cells with minimal effects on T
effector cells. This is an important finding that validates the
mechanistic approach of NKTR-358 for the treatment of autoimmune
diseases, and provides a strong rationale for its ongoing clinical
development," said Dr. Richard
Furie, NKTR-358 key investigator and Chief, Division of
Rheumatology, Northwell Health and Professor, Zucker School of Medicine at Hofstra/Northwell.
"NKTR-358 preferentially binds to the high affinity trimeric
receptor on T regulatory cells resulting in the downregulation of
function and proliferation of T effector cells," said Jonathan
Zalevsky, Ph.D., Chief Research & Development Officer at
Nektar. "The findings in the Journal of Translational
Autoimmunity deepen our understanding of the pharmacology of
NKTR-358 and, together with the early promising clinical data,
provide strong support for continued testing as a new therapeutic
for patients with diseases that have an imbalance of T lymphocyte
subsets leading to autoimmunity. We look forward to the continued
progress of multiple NKTR-358 studies across numerous autoimmune
and inflammatory diseases by our partner, Eli Lilly."
In the study, researchers investigated NKTR-358's selectivity
for Tregs, receptor-binding properties, ex vivo and in
vivo pharmacodynamics, ability to suppress T effector cell
proliferation in vivo and functional activity in a murine
model of systemic lupus erythematosus (SLE).
Key findings are summarized below:
- A single administration of NKTR-358 in mice promotes greater
Treg expansion compared with multiple administrations of native
IL-2, demonstrating enhanced specificity towards Treg induction and
improved pharmacokinetics in comparison with native IL-2.
- In a murine model of SLE, treatment with NKTR-358 maintained
elevated Tregs for the duration of treatment and ameliorated
disease progression.
- Tregs isolated from NKTR-358-treated mice displayed a sustained
and higher suppression of T effector cell proliferation versus
those from vehicle-treated mice.
- Repeated NKTR-358 dosing in non-human primates over six months
demonstrated expansion of Tregs following each dose. Importantly,
no anti-drug antibodies were detected during the six months of
dosing, indicating that NKTR-358 does not induce immunogenicity
while maintaining its pharmacologic effects over time.
Phase 1b data presented at the
European Congress of Rheumatology (EULAR) in June 2020 showed that NKTR-358 was safe and well
tolerated in patients with mild-to-moderate SLE and led to a marked
and selective, dose-dependent expansion of Tregs that was
maintained over multiple administrations. Additional Phase
1b data from the study presented at
the annual American College of Rheumatology (ACR) meeting in
November 2020 included key biomarkers
of Treg function and assessment of disease characteristics in mild
to moderate SLE patients.
As part of the broad development program for NKTR-358, Nektar's
partner, Eli Lilly & Co., is conducting a Phase 2 study in
patients with SLE, a Phase 2 study in patients with ulcerative
colitis, as well as two separate Phase 1b studies in patients with atopic dermatitis and
psoriasis.
A link to the publication can be found here.
About NKTR-358 (LY3471851)
Autoimmune and inflammatory
diseases cause the immune system to mistakenly attack and damage
healthy cells in a person's body. A failure of the body's
self-tolerance mechanisms enables the formation of the pathogenic T
lymphocytes that conduct this attack. NKTR-358 is a potential
first-in-class therapeutic that may address an underlying immune
system imbalance in people with many autoimmune conditions. It
targets the interleukin (IL-2) receptor complex in the body in
order to stimulate proliferation of inhibitory immune cells known
as regulatory T cells. By activating these cells, NKTR-358 may act
to bring the immune system back into balance. Nektar entered into a
strategic collaboration with Lilly in 2017 to develop and
commercialize NKTR-358.
NKTR-358 is being developed by Lilly for a number of autoimmune
and inflammatory diseases. A Phase 2 study of NKTR-358 is underway
in adults with systemic lupus erythematosus (ISLAND-SLE)
(NCT04433585). A Phase 2 study of NKTR-358 is also underway in
patients with moderate to severe ulcerative colitis (INSTRUCT-UC)
(NCT04677179). The investigational therapy is also currently being
evaluated in two separate Phase 1b studies in patients
with atopic dermatitis (NCT04081350) and psoriasis
(NCT04119557).
About Nektar
Nektar Therapeutics is a
biopharmaceutical company with a robust, wholly owned R&D
pipeline of investigational medicines in oncology, immunology, and
virology as well as a portfolio of approved partnered medicines.
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.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains
forward-looking statements which can be identified by words such
as: "may," "design," "develop," "potential" and similar references
to future periods. Examples of forward-looking statements include,
among others, statements we make regarding the therapeutic
potential of, and future development plans for, NKTR-358.
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-358 are based on preclinical and clinical
findings and observations and are subject to change as research and
development continue; (ii) NKTR-358 is an investigational agent and
continued research and development for this drug candidate is
subject to substantial risks, including negative safety and
efficacy findings in ongoing clinical studies (notwithstanding
positive findings in earlier preclinical and clinical studies);
(iii) NKTR-358 is currently in clinical development and the risk of
failure is high and can unexpectedly occur at any stage prior to
regulatory approval; (iv) the timing of the commencement or end of
clinical trials and the availability of clinical data 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) 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) 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 14, 2021. 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:
Vivian Wu of Nektar Therapeutics
628-895-0661
For Media:
Dan Budwick of 1AB
973-271-6085
dan@1abmedia.com
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