Etanercept biosimilar (Qilu Pharmaceutical)

– 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

- New proteomic analyses show that rezpegaldesleukin increases the protein levels of immune-regulating pathways while reducing specific serum proteins known to be elevated in patients with atopic dermatitis - SAN FRANCISCO, Sept. 25, 2024 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced several presentations for rezpegaldesleukin (REZPEG) at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. In addition to two trial-in-progress posters, new proteomic analyses were presented that showcases a unique serum proteomic profile in patients with atopic dermatitis (AD). "As an agonist, REZPEG has a differentiated mechanism of action which is demonstrated by its unique proteomic profile presented today at EADV 2024," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "The data show that REZPEG induces important immunoregulatory pathways, such as IL-10, a key anti-inflammatory cytokine. In addition, REZPEG reduced specific cytokines and chemokines which are known to be elevated in patients with atopic dermatitis and other atopy diseases, including IL-15, CCL22, CX3CL1, and IL-19. These data provide a greater mechanistic understanding of how treatment with REZPEG led to dose-dependent efficacy in the Phase 1b study over the 12-week treatment period, including its rapid onset of action, and it also provides insight into pathways that could result in the sustained efficacy that was observed in that study even after treatment was removed." REZPEG is a novel first-in-class regulatory T (Treg) cell stimulator designed to address the imbalance in the immune system underlying autoimmune disorders and chronic inflammatory conditions. REZPEG works by targeting the IL-2 receptor complex and preferentially stimulating the proliferation of Treg cells without stimulating cytotoxic CD8+ T and CD4+ T cells, which drive autoimmune disease, to restore immune balance. REZPEG is currently being evaluated in two Phase 2b studies, one in moderate-to-severe AD and one in severe to very severe alopecia areata (AA). Nektar expects topline data from the AD study in the first half of 2025 and topline data from the AA study in the middle of 2025. "In recent years, significant progress has been made in the treatment of atopic dermatitis. However, some patients still do not respond to the available biologics and small molecules. Therefore, there is a strong need for molecules with different mechanisms of action, particularly those that are immunoregulatory rather than immunosuppressive," said Spyridon Gkalpakiotis, M.D., Ph.D., MBA, a principal investigator on the Phase 2b study of rezpegaldesleukin in atopic dermatitis and Professor in the Department of Dermatovenerology 3FM CU and UHKV at the University Hospital Královské Vinohrady, Prague, Czech Republic. "My colleagues and I are excited to be a part of a study that can potentially offer the hope of durable effects and long-term remission which could change the paradigm of how we treat patients with atopic dermatitis." The poster presentations are available for download at . Key details and takeaways from the presentations are as follows: Abstract 5560/ePoster P0662: "Serum proteomic biomarker analysis of the interleukin-2 receptor pathway agonist rezpegaldesleukin in patients with atopic dermatitis", Yu, et al. Patients with moderate-to-severe AD received 12 or 24 µg/kg REZPEG or placebo once every two weeks for 12 weeks. The Olink proteomics platform was used to measure the levels of soluble serum proteins from patients at baseline and throughout the induction period. REZPEG modulated Treg pathways and those involving lymphocyte immune homeostasis, MHC expression and regulation, ectodomain shedding of cell surface receptors, as well as cellular migration and adhesion processes. As an IL-2 receptor pathway agonist, REZPEG demonstrated a unique serum proteomic profile in AD patients, reducing the expression of serum proteins known to be elevated in patients with AD and demonstrated an effect on the expression levels of known targets for current AD therapy. Abstract 4505/ePoster P0600 (Trial in Progress): "A Phase 2b, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled, International, Multicenter, Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in Adults with Moderate-to-Severe Atopic Dermatitis", Gkalpakiotis, et al. The Phase 2b trial is enrolling biologic and JAK-inhibitor naïve adults with moderate-to-severe AD. The primary outcome is reduction in Eczema Area and Severity Index (EASI) score from baseline at the end of the treatment induction phase. Secondary and exploratory endpoints include reduction in Investigator's Global Assessment (IGA) AD score, affected total body surface area (BSA) improvement, as well as safety and tolerability. Abstract 2459/ePoster P2080 (Trial in Progress): "A Phase 2b Study Evaluating the Efficacy and Safety of Single Agent Rezpegaldesleukin, an Interleukin-2 Receptor (IL-2R) Pathway Agonist, in the Treatment of Severe to Very Severe Alopecia Areata", Reich, et al. The Phase 2b trial is enrolling JAK-inhibitor naïve patients with severe to very severe alopecia areata. The primary endpoint is percent change from baseline in Severity Alopecia Tool (SALT) score at the end of the treatment period. Secondary and exploratory endpoints include percent change from baseline in SALT score at other assessed timepoints, safety and tolerability, as well as various patient reported outcomes. About REZPEG 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. REZPEG 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, REZPEG may act to bring the immune system back into balance. REZPEG 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 (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," 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 are investigational agents and continued research and development for these drug candidates 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 health epidemics, including the COVID-19 pandemic, 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) we may not achieve the expected cost savings we expect from our 2022 corporate restructuring and reorganization plan or our 2023 cost restructuring plan and we may undertake additional restructuring and cost-saving activities in the future, (vi) 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 (vii) 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 646-461-6387 [email protected] 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