Initial data presented earlier this year at the
"In our data presented at ACR 2020, we were excited to see that NKTR-358 demonstrated a dose-dependent reduction in CLASI-A composite clinical scores in patients with mild-to-moderate SLE after only 3 treatment cycles. Complementing these clinical results, we also observed dose-dependent biomarker changes associated with Treg activation including increases in Treg functional markers, changes in DNA methylation of the FoxP3 locus, and increased expression of Treg functional genes," said
The randomized, double-blind, multiple-ascending dose Phase 1b data from the study being presented at 2020 ACR evaluated safety, pharmacokinetics (PK) and pharmacodynamics (PD) in a total of 48 SLE patients across 4 separate ascending dose cohorts who received subcutaneous Q2W doses of NKTR-358 (n=9 per cohort) or placebo (n=3 per cohort). Subjects were treated for a total of six weeks.
Key conclusions from today's data presentation at ACR 2020 include:
- NKTR-358 was safe and well tolerated with a similar safety profile for single and repeat doses in patients with mild-to-moderate SLE as was observed in healthy volunteers from a prior Phase 1 study
- A selective, dose-dependent expansion of CD25bright Tregs was observed, which was maintained through multiple NKTR-358 administrations
- Treg induction was further supported by a correlation between the number of Tregs and the extent of demethylated FoxP3
- Increases in Treg activation markers (CD25, Helios, and CTLA-4) and genes associated with Treg regulation were observed with NKTR-358
- Low-level increases in NK cell numbers occurred in most patients at the highest NKTR-358 dose; the CD56bright NK cell population was more sensitive than the CD56dim
- A dose-dependent reduction in CLASI-A1 score was seen with NKTR-358 treatment, which supports further exploration in patients with moderate-to-severe SLE
- No observed changes in SLEDAI or joint scores were noted due to the short treatment duration in this study
A Phase 2 trial of NKTR-358 in patients with SLE (NCT04433585) as well as two separate Phase 1b studies in patients with atopic dermatitis (NCT04081350) and psoriasis (NCT04119557) are currently recruiting.
Nektar will host a call today for analysts and investors to review the data presented at ACR 2020. Details of the call are as follows:
Date and Time: Wednesday, November 4, 2020 at
Dial- in: (877) 881-2183 (toll-free) or (970) 315-0453 (access code 7083115)
Investors and analysts can view slides and listen to the live audio webcast of the presentation at https://edge.media-server.com/mmc/p/yppmbgt9. The event will also be available for replay for two weeks on the company's website, www.nektar.com.
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 as a self-administered injection 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). The investigational therapy is also currently being evaluated in two separate Phase 1b studies in patients with atopic dermatitis (NCT04081350) and psoriasis (NCT04119557).
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "may," "can," "develop," "will," and similar references to future periods. Examples of forward-looking statements include, among others, statements we make concerning the therapeutic potential of NKTR-358, and future development plans for this drug candidate. 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) the extent and duration of the impact of the COVID-19 pandemic on our business, regulatory efforts, research and development, clinical trials (including those being led by us and our partner), and corporate development activities will depend on future developments that are highly uncertain and cannot be accurately predicted, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the
1. CLASI-A: cutaneous lupus erythematosus disease area and severity index - activity
Dan Budwick of 1AB
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