Etanercept biosimilar (Qilu Pharmaceutical)

- 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: . 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 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 SOURCE Nektar Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– Relapse-free/progression-free survival for NKTR-255 plus CD19-22 CAR-T cell therapy at 12 months was double that of historical controls (67% vs 38%) – – Eight of nine patients achieved complete remission, all without detectable MRD – SAN FRANCISCO, Oct. 17, 2024 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the publication of the first clinical data from a Phase 1 study evaluating NKTR-255 in combination with an autologous bispecific chimeric antigen receptor (CAR)-T cell therapy targeting CD19 and CD22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in Blood, the peer-reviewed medical journal of the American Society of Hematology. NKTR-255 is a novel IL-15 receptor agonist currently being studied in clinical trials in combination with cellular therapies and immune checkpoint inhibitors. NKTR-255 has shown in previous clinical studies that it can proliferate a range of immune cells and augment lymphocyte trafficking.1,2 The data published in Blood showed favorable efficacy with eight out of nine patients (89%) whom successfully received CAR19-22 followed by NKTR-255 achieving measurable residual disease (MRD) negative remission. The study further demonstrated that, at 12 months, relapse-free/progression-free survival for NKTR-255 in combination with the CD19-22 CAR-T cell therapy was double that of historical controls (67% vs 38%). "We are encouraged by these first clinical data that clearly demonstrate the ability of NKTR-255 to potentiate CAR-T cell therapy," said Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar. "Data showed NKTR-255 in combination with CD19-22 CAR-T cell therapy resulted in a 67% 12-month relapse-free survival rate in relapsed or refractory B-ALL and investigators observed significant increases in proinflammatory cytokines and chemokines which suggest lymphocyte trafficking to tissues." The Phase 1 single-center, single-arm dose-escalation study was conducted by Stanford Medicine and evaluated NKTR-255 in combination with CD19-22 CAR-T cell therapy in patients with relapsed or refractory B-ALL (NCT03233854). "While CAR-T cell therapies have transformed the treatment landscape for B-cell malignancies, there remains a significant unmet need to drive durable treatment outcomes as relapse occurs in the majority of patients," said David Miklos, MD, Chief of BMT and Cell Therapy Program at Stanford Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy. The primary outcomes of this study were feasibility and safety. Secondary endpoints were assessed for patients who received NKTR-255 (n=9) and included pharmacokinetics of NKTR-255 as measured by IL-15 levels in blood and efficacy as measured by remission free survival (RFS). Exploratory endpoints included cytokine profiling, CAR19-22 expansion in blood, bone marrow, and cerebrospinal fluid (CSF), and long-term CAR-T persistence. Key findings are summarized below: No dose-limiting toxicities related to NKTR-255 were observed. The most common adverse events in patients receiving NKTR-255 in combination with the CD19-22 CAR-T cell therapy were fevers, chills, and myelosuppression, which were either self-limiting or manageable with supportive care. The toxicities observed with the combination treatment were similar to those seen after CD19-22 CAR-T cell therapy alone. Cytokine and chemokine profiling showed significant increases in IL-15 levels. Increase in CXCL9 and CXCL10 were associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood, and ten-fold increases CAR-T cells in CSF, suggesting lymphocyte trafficking to tissue. Favorable efficacy was observed in patients with relapsed or refractory B-ALL treated with NKTR-255 in combination with CD19-22 CAR-T. Eight out of nine patients achieved complete remission with or without hematologic recovery, all without detectable MRD. Compared to Stanford's control group previously treated with the CD19-22 CAR-T cell therapy, NKTR-255 when added to the cell therapy increased the 12-month relapse free survival from 38% to 67%. The median RFS for the CAR T cell only cohort was 3.9 months. For the cohort treated with NKTR-255 and the CD 19-22 CAR-T cell therapy, the median RFS has not been reached with over 14 months of follow up. Only three patients who received combination therapy (33%) relapsed, suggesting administration of NKTR-255 to the CD19-22 CAR-T cell therapy helps prevent early disease recurrence. The full citation of this article can be accessed here (Volume 144, Issue 16, Pages 1649-1753). About NKTR-255 NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body's innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response. In addition to studies in combination with CAR T cell therapies, NKTR-255 is being studied in a Phase 1 clinical trial sponsored by AbelZeta Pharma, Inc., which is evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer (NCT05676749). The JAVELIN Bladder Medley study (NCT05327530), sponsored by Merck KGaA, is also ongoing to evaluate NKTR-255 in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma.(NCT05327530) 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 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," "expect," "develop," "potential," "advance," "anticipate," "can," 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, NKTR-255. 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 future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) NKTR-255 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 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 For Media: David Rosen of Argot Partners (212) 600-1902 [email protected] Hirayama A. et al. Pharmacodynamic Analysis of CAR-T Cell Persistence in Patients with Hematologic Malignancies Treated with NKTR-255, an IL-15 Receptor Agonist That Enhances CD8 + T-Cells: Preliminary Results from a Phase 1 Study. Poster presented at: 63rd ASH Annual Meeting; Dec 11-13, 2021; Atlanta, GA Altan M. et al. NKTR-255+cetuximab in patients with solid tumors: interim safety and efficacy results from the phase 1b dose-escalation study. Poster presented at: SITC 2021; Nov 10-14, 2021; Washington, D.C. SOURCE Nektar Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED