SAN FRANCISCO, May 18, 2021 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR) today announced the publication of
preclinical data from its second major immuno-oncology cytokine
program, NKTR-255, in the Journal for ImmunoTherapy of
Cancer (JITC). NKTR-255 is a novel recombinant human
Interleukin-15 (rhIL-15) receptor agonist designed to activate the
IL-15 pathway to expand both natural killer (NK) cells and memory
CD8+ T cell populations. The published data demonstrate that
NKTR-255 retains the full spectrum of IL-15 biology but with
improved pharmacologic properties and anti-tumor activity versus
other rhIL-15 agonists. These preclinical findings support Nektar's
robust clinical development program for NKTR-255 in patients with
hematologic malignancies and solid tumors.
"These findings published today in the Journal for
ImmunoTherapy of Cancer demonstrate IL-15's mechanism of
action for engaging natural killer cell biology for the treatment
of cancers," said Dr. Amita Patnaik,
MD, FRCP(C), Co-Director of Clinical Research at the START Center
for Cancer Care and a core investigator on the NKTR-255 clinical
development program. "NKTR-255 may represent a particularly potent
immunotherapeutic, and the data provide a strong rationale for
clinical development."
"The findings in JITC describe the foundational science
behind NKTR-255 and support its clinical advancement in both liquid
and solid tumors," said Jonathan Zalevsky, Ph.D., Chief
Research & Development Officer at Nektar. "We look forward
to results from our two Phase 1/2 studies designed to evaluate
NKTR-255 as a monotherapy as well as in combination with leading
antibody-dependent cellular toxicity compounds, rituximab and
daratumumab in hematological malignancies, and cetuximab in solid
tumors."
Researchers analyzed in vitro pharmacological properties
of rhIL-15, NKTR-255 and precomplexed IL-15 cytokines
(rhIL-15/IL-15Ra and rhIL-15 N72D/IL-15Rα Fc) in receptor binding,
cell signaling and cell function assays. In vivo
pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the
cytokines were evaluated in normal mice, and immunomodulatory
effect and anti-tumor activity were assessed in a model of
lymphoma.
Key findings are summarized below:
- NKTR-255 maintained a similar receptor binding profile to that
of rhIL-15, as compared to precomplexed IL-15 agonists.
- In vivo, NKTR-255 exhibited a PK profile with reduced
clearance and a longer half-life (clearance: 2.31 mL/hour/kg;
effective half-life: 15.2 hours) relative to rhIL-15 (clearance:
507 mL/hour/kg; effective half-life: 0.168 hours); NKTR-255 also
demonstrated prolonged IL-15R engagement in lymphocytes compared
with only transient engagement observed for rhIL-15 and
precomplexed rhIL-15 N72D/IL-15Rα Fc.
- NKTR-255 was shown to provide a more durable and sustained
effect on proliferation and activation of NK and CD8+ T cells than
precomplexed cytokines.
- The properties of NKTR-255 promoted elevations in functionally
competent cytotoxic NK cells in the tumor microenvironment and
overall translated into increased survival rates and superior
antitumor activity in a B-cell lymphoma model versus the
precomplexed cytokines.
NKTR-255 is currently being evaluated in multiple clinical
studies in both hematologic malignancies and solid tumors as a
monotherapy and in combination with agents that induce
antibody-dependent cellular toxicity (ADCC). In the hematological
setting, NKTR-255 is being tested in a Phase 1b/2 clinical study as monotherapy and in
combination with rituximab or daratumumab in patients with multiple
myeloma (MM) and non-Hodgkin's lymphoma (NHL). It is also being
evaluated in a Phase 1b/2 solid tumor
trial in combination with cetuximab for the treatment of colorectal
cancer (CRC) and head and neck squamous cell carcinoma
(HNSCC).
In November 2020, Nektar reported
encouraging early data from the NKTR-255 Phase 1/2 study in
patients with relapsed/refractory hematologic malignancies at the
2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting.
NKTR-255 was administered intravenously (IV) every three weeks
(Q3W), a similar dosing to that of checkpoint antibodies. These
data indicated that NKTR-255 was
biologically active and demonstrated consistent expansion of
lymphocytes, with durable and sustained increases in NK and CD8+ T
cells in the highly refractory population of patients with MM and
NHL. NKTR-255 exhibited a long half-life and was well tolerated
with low-grade, cytokine-related AEs that were transient in nature
and easily managed. No anti-drug antibodies were
reported.
About NKTR-255
NKTR-255 is a novel polyethylene glycol
(PEG)-conjugate of recombinant human Interleukin-15 (rhIL-15),
which was designed to retain all known receptor binding
interactions of the IL-15 molecule.
NKTR-255 is uniquely designed to overcome the challenges of
recombinant IL-15 and other IL-15 agonists, which are rapidly
cleared from the body and have shown diminishing response to
successive doses. Through an extended circulating half-life and
optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex,
NKTR-255 enhances functional NK cell populations and formation of
long-term CD8+ mediated immunological memory, which may lead to
sustained anti-tumor immune response.
The full citation of this article can be accessed at: Miyazaki
T, Maiti M, Hennessy M, et al. NKTR-255, a novel polymer-conjugated
rhIL-15 with potent antitumor efficacy. Journal for ImmunoTherapy
of Cancer 2021;0:e002024. doi:10.1136/jitc-2020-002024.
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," "potential," "provide," "support" 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-255
in both liquid and solid tumors. 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-255 are based on preclinical and
clinical findings and observations and are subject to change as
research and development continue; (ii) NKTR-255 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-255 is in early
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
or competitive factors; (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
View original content to download
multimedia:http://www.prnewswire.com/news-releases/nektar-therapeutics-announces-its-first-publication-of-preclinical-data-highlighting-anti-tumor-properties-of-il-15-agonist-nktr-255-in-the-journal-for-immunotherapy-of-cancer-jitc-301293169.html
SOURCE Nektar Therapeutics