The data, which were presented at the 2019 Annual Meeting of the
NKTR-358 is designed to treat autoimmune and inflammatory conditions by correcting the immune system imbalance that results from reduced numbers and impaired function of immune-regulating Treg cells. NKTR-358 works by targeting the interleukin-2 receptor complex to stimulate the proliferation and activation of Treg cells. NKTR-358 was discovered by Nektar and is being co-developed and commercialized in partnership with
"We're pleased to report that final results from our first-in-human Phase 1a study continue to support the positive safety and tolerability profile of NKTR-358, while reinforcing its selective and measurable impact on the numbers, expansion and activation of regulatory T cells or Tregs," said
The data were presented today in a poster titled "Selective induction of functional regulatory T-cells in healthy volunteers by NKTR-358, a novel IL-2 conjugate Treg stimulator, in development for the treatment of autoimmune diseases", by Dr.
The double-blind, single-ascending dose Phase 1a study evaluated 100 healthy volunteers who received subcutaneous doses of NKTR-358 ranging from 0.3 to 28.0 µg/kg and were followed for 50 days after dosing.
Key highlights from today's data presentation include:
- NKTR-358 was safe and well tolerated in this first-in-human study consistent with prior reported results.
- No anti-drug antibodies were detected.
- Final data show dose-proportional pharmacokinetics, with maximal concentrations reached in 5-7 days and prolonged exposure with an estimated half-life of 8-11 days.
- New data confirm that single-ascending doses of NKTR-358 led to marked dose-dependent and sustained increases in the absolute numbers, percentages and proliferation of circulating FoxP3+CD25bright Treg cells. In addition,
- At the highest dose tested of NKTR-358, 28.0 µg/kg, the mean percentage of Ki67+ CD25bright Tregs was 6-fold above baseline.
- NKTR-358 increased the expression of Treg activation markers.
- Epigenetic analysis of immune cells demonstrated a significant increase in demethylated FOXP3 gene following NKTR-358 treatment at 28.0 µg/kg, further reinforcing that NKTR-358 is expanding true Tregs.
- NKTR-358 induced dose-dependent changes in other genes associated with Treg regulation.
- NKTR-358 was not associated with any measurable changes in numbers and percentages of conventional CD4+ and CD8+ T cells (Tcons) at all doses and low-level increases of natural killer (NK) cell numbers was observed at highest doses tested.
A copy of the poster presentation of NKTR-358 data is available on Nektar's corporate website at https://www.nektar.com/download_file/722/0.
NKTR-358 is also being evaluated in a multiple ascending dose (MAD) study in patients with systemic lupus erythematosus and two additional double-blind, randomized, placebo-controlled Phase 1b studies in adults with psoriasis and atopic dermatitis. For more information, please visit clinicaltrials.gov and search for NCT03556007 (SLE trial), NCT04119557 (Psoriasis trial) and NCT04081350 (Atopic Dermatitis trial).
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 resolution therapeutic that may address this underlying immune system imbalance in people with different 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, 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 as a self-administered injection for a number of autoimmune and inflammatory diseases.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "potential," "design," "continue," "may," and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding the expected benefits of NKTR-358, the ability to obtain useful data from the Phase 1a and 1b clinical studies of NKTR-358, and the future clinical 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) NKTR-358 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 Phase 1b clinical study notwithstanding positive findings in prior studies; (ii) clinical study outcomes, including the Phase 1b clinical study outcome of NKTR-358, remain very unpredictable and it is possible that a clinical study could fail due to efficacy, safety or other important clinical findings; (iii) 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, delays caused by our collaboration partners, and enrollment competition; (iv) scientific discovery of new therapeutics is an inherently uncertain process and the future success of applying our technology platform to potential new drug candidates (such as NKTR-358) is therefore highly uncertain and unpredictable; (v) patents may not issue from our patent applications for NKTR-358, 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 Nektar's Quarterly Report on Form 10-Q filed with the
*NKTR-358 is referred to as LY3471851 under Lilly-sponsored studies.
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