- Data from multiple Phase 1b studies in inflammatory skin conditions
demonstrate durable dose-dependent improvements in
physician-assessed disease activity and patient-reported outcomes
-
- Biomarker analyses demonstrate plurality of
Treg-mediated pathways with potential effect on tissue resident
memory T cell populations resulting in sustained efficacy seen in
the antigen challenged mouse model and in clinical trials -
SAN
FRANCISCO, Oct. 29, 2024 /PRNewswire/ -- Nektar
Therapeutics (Nasdaq: NKTR), today announced the publication of
peer-reviewed data from two Phase 1b
studies in Nature Communications highlighting the efficacy,
safety, and tolerability of rezpegaldesleukin in patients with
atopic dermatitis (AD) and psoriasis (PsO).
Rezpegaldesleukin is a first-in-class interleukin-2 receptor
(IL-2R) agonist that enhances the activity of regulatory T cells
(Tregs) with promising dose-dependent clinical activity across
multiple physician-assessed and patient-reported endpoints for AD
and PsO.
Results from the Phase 1b studies
showed that rezpegaldesleukin safely and dose-dependently increased
Tregs and rapidly improved measurable exploratory disease outcomes
that are largely durable for at least 36 weeks after ceasing
treatment.
"These promising findings clinically validate, for the first
time, the Treg hypothesis – that restoring Treg function through a
central pathway of IL‑2R-driven Treg rescue can have disease
remittive potential across a variety of chronic inflammatory skin
diseases," said Jonathan Silverberg,
M.D., Ph.D., Professor of Dermatology at George Washington University School of Medicine and
lead study author. "Newer evidence suggests that diseases
like atopic dermatitis are not exclusively Th2-mediated. These
results show that rezpegaldesleukin can act on multiple
disease-driving pathways and is uniquely poised to address a
diversity of immunopathologies."
"The exciting clinical cross-indication efficacy here is
buttressed by serum biomarker analysis demonstrating that
rezpegaldesleukin can modulate multiple immunoregulatory
pathways to provide rapid onset and duration of efficacy" said
Jonathan Zalevsky, Ph.D., Chief
Research & Development Officer at Nektar. "These findings
further validate our therapeutic approach of using a Treg
stimulator to dampen inflammatory responses and simultaneously
restore immune balance in patients with chronic inflammatory skin
diseases. We look forward to reporting topline data next year from
our two Phase 2b rezpegaldesleukin
studies in atopic dermatitis and alopecia areata."
Key findings are summarized below:
- Rezpegaldesleukin was evaluated in two randomized,
double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe
atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis
(PsO) (NCT04119557)
- Rezpegaldesleukin is safe and well-tolerated and demonstrates
consistent pharmacokinetics in participants receiving subcutaneous
doses of 10 to 12 μg/kg or 24 μg/kg once every 2 weeks for 12
weeks, meeting the primary and secondary objectives of each
study
- AD patients receiving high dose rezpegaldesleukin demonstrate
an 83% improvement in EASI score after 12 weeks of treatment EASI
improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained
for 36 weeks after treatment discontinuation in 71% and 80% of week
12 responders, respectively
- The clinical improvements are accompanied by sustained
increases in CD25bright Tregs
- Serum proteomic biomarkers demonstrated rezpegaldesleukin's
ability to engage multiple immunoregulatory mechanisms to
facilitate immune homeostasis, which may indicate a potential
mechanism of attenuating Th1, Th2, and Th17 responses by restoring
the balance of Tregs.
- Results validate the role of IL-2-induced Treg proliferation
and activation in the AD treatment paradigm, and support the
advancement of rezpegaldesleukin in the Phase 2b study in AD.
- The delayed-type hypersensitivity (DTH) mouse model and the
profound reduction in serum IL-15 levels in atopic dermatitis
patients treated with rezpegaldesleukin provides mechanistic
insight for the durable efficacy that persists for months following
treatment
The full citation of this article can be accessed at:
https://rdcu.be/dX8lr.
About Rezpegaldesleukin
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.
Rezpegaldesleukin is a potential first-in-class resolution
therapeutic that may address this underlying immune system
imbalance in people with many autoimmune and inflammatory
conditions. It targets the interleukin-2 receptor complex in the
body in order to stimulate proliferation of powerful inhibitory
immune cells known as regulatory T cells. By activating these
cells, rezpegaldesleukin may act to bring the immune system
back into balance.
Rezpegaldesleukin is being developed as a self-administered
injection for a number of autoimmune and inflammatory diseases. It
is wholly-owned by Nektar Therapeutics.
About Nektar Therapeutics
Nektar Therapeutics is a clinical-stage biotechnology
company focused on developing treatments that address the
underlying immunological dysfunction in autoimmune and chronic
inflammatory diseases. Nektar's lead product candidate,
rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class
regulatory T cell stimulator being evaluated in two Phase
2b clinical trials, one in atopic
dermatitis and one in alopecia areata. Our pipeline also includes a
preclinical candidate NKTR-0165, which is a bivalent tumor necrosis
factor receptor type II agonist antibody. Nektar, together with
various partners, is also evaluating NKTR-255, an investigational
IL-15 receptor agonist designed to boost the immune system's
natural ability to fight cancer, in several ongoing clinical
trials. Nektar is headquartered in San
Francisco, California. For further information,
visit www.nektar.com and follow us on LinkedIn.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements which can
be identified by words such as: "will," "can," "expect," "develop,"
"potential," "advance," "anticipate," and similar references to
future periods. Examples of forward-looking statements include,
among others, statements regarding the therapeutic potential of,
and future development plans for rezpegaldesleukin.
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 rezpegaldesleukin are based on preclinical and
clinical findings and observations and are subject to change as
research and development continue; (ii) rezpegaldesleukin 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 future clinical studies
(notwithstanding positive findings in earlier preclinical and
clinical studies); (iii) rezpegaldesleukin is 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 challenges
caused by 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 August 9,
2024. 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
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