The goal of this Phase 1 clinical study is test tumor infiltrating lymphocytes (known as C-TIL051) with NKTR-255 and anti-PD1 therapy for subjects with refractory non-small cell lung cancer.
The purpose of this study is to:
1. Test the safety and ability for subjects to tolerate the TIL therapy
2. Measure to see how the NSCLC responds to the TIL therapy
Participants will be asked to:
* Provide a tumor sample prior to the start of any treatment which will be used to make the C-TIL051.
* Receive standard of care treatment until their lung cancer no longer responds
* When necessary, the C-TIL051 will be manufactured by the sponsor and sent back to the site
* Subject will then receive chemotherapy (called lymphodepletion) for 3 days followed by 2 days of rest
* C-TIL051 will then be infused on day 0 followed by NKTR-255 (IL-15) about 12 to 24 hours later
* Pembrolizumab will be administered every 3 weeks for up to 2 years
NKTR-255 is a novel polymer-conjugated human IL-15 receptor agonist molecule designed to increase the proliferation and survival of memory CD8+ T cells and enhance the formation of long-term immunological memory which may lead to sustained anti-cancer immune response. The combination of NKTR 255 and TIL's could improve proliferation and persistence of cellular therapies leading to enhanced anti-tumor activity.

Start Date29 Feb 2024

Sponsor / Collaborator

AbelZeta Pharma, Inc.

[+1]

NCT05632809

/ RecruitingPhase 2IIT

REStoring lymphoCytes Using NKTR-255* After chemoradiothErapy in Solid Tumors (RESCUE)

To learn about the effects of the investigational drug NKTR-255 in combination with the standard drug durvalumab on locally advanced NSCLC when given after CRT.

Start Date10 Jan 2023

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT05664217

/ TerminatedPhase 2/3

A Phase 2/3, Randomized, Double Blind, Placebo-controlled, Multicenter Study of NKTR-255 vs Placebo Following CD19-directed CAR-T Cell Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma

This study will evaluate the safety and efficacy of NKTR-255 following CD19-directed chimeric antigen (CAR)-T cell therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL).
NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. T cells are infection fighting blood cells that can kill tumor cells. Chimeric antigen (CAR)-T cell product consists of genetically engineered T-cells, modified to recognize CD19, a protein on the surface of cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19-positive cancer cells. Giving NKTR-255 following the treatment with CD19 CAR-T cell therapy may work better in treating large B-cell lymphoma than either drug alone.

Start Date23 Dec 2022

Sponsor / Collaborator

Nektar Therapeutics

100 Clinical Results associated with NKTR-255

100 Translational Medicine associated with NKTR-255

100 Patents (Medical) associated with NKTR-255

Literatures (Medical) associated with NKTR-255

01 Dec 2024·Molecular Therapy: Oncology

Combinatorial immunotherapy of anti-MCAM CAR-modified expanded natural killer cells and NKTR-255 against neuroblastoma

Article

Author: Cairo, Mitchell S. ; Mo, Xiaokui ; Liao, Yanling ; Overwijk, Willem W. ; Cairo, Mitchell S ; Cripe, Timothy P. ; Ayello, Janet ; Luo, Wen ; Gardenswartz, Aliza ; Rosenblum, Jeremy M ; Marcondes, A. Mario ; Tian, Meijuan ; Marcondes, A Mario ; Overwijk, Willem W ; Cripe, Timothy P ; Chu, Yaya ; Lee, Dean A. ; Rosenblum, Jeremy M. ; Lee, Dean A ; Hoang, Hai

Pediatric patients with recurrent metastatic neuroblastoma (NB) have a dismal 5-year survival. Novel therapeutic approaches are urgently needed. The melanoma cell adhesion molecule (MCAM/CD146/MUC18) is expressed in a variety of pediatric solid tumors, including NB, and constitutes a novel target for immunotherapy. Here, we developed a chimeric antigen receptor (CAR) expressing natural killer (NK) cell-targeting MCAM by non-viral electroporation of CAR mRNA into ex vivo expanded NK cells. Expression of anti-MCAM CAR significantly enhanced NK cell cytotoxic activity compared to mock NK cells against MCAM^high but not MCAM^low/knockout NB cells in vitro. Anti-MCAM-CAR-NK cell treatment significantly decreased tumor growth and prolonged animal survival in an NB xenograft mouse model. NKTR-255, a polymer-conjugated recombinant human interleukin-15 agonist, significantly stimulated NK cell proliferation and expansion and further enhanced the in vitro cytotoxic activity and in vivo anti-tumor efficacy of anti-MCAM-CAR-NK cells against NB. Our preclinical studies demonstrate that ex vivo expanded and modified anti-MCAM-CAR-NK cells alone and/or in combination with NKTR-255 are promising novel alternative therapeutic approaches to targeting MCAM^high malignant NB.

17 Oct 2024·BLOOD

A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia

Article

Author: Arai, Sally ; Weng, Wen-Kai ; Sidana, Surbhi ; Dahiya, Saurabh ; Shizuru, Judith ; Mavroukakis, Sharon ; Kennedy, Vanessa ; Muffly, Lori ; Marcondes, A. Mario ; Kramer, Anne Marijn ; Shiraz, Parveen ; Jackson, Clayton ; Frank, Matthew J. ; Jeyakumar, Nikeshan ; Liedtke, Michaela ; Rezvani, Andrew ; Lowsky, Robert ; Johnston, Laura ; Sahaf, Bita ; Tagliaferri, Mary ; Feldman, Steven ; Negrin, Robert ; Agarwal, Neha ; Smith, Melody ; Mikkilineni, Lekha ; Bharadwaj, Sushma ; Kuo, Adam ; Cancilla, Juancarlos ; Srinagesh, Hrishikesh ; Kanegai, Alyssa ; Lee, Zachary ; Hamilton, Mark ; Mackall, Crystal ; Hosoya, Hitomi ; Miklos, David ; Egeler, Emily

Abstract:

Although chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed/refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, 9 of whom successfully received CAR19-22 followed by NKTR-255. There were no dose-limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with 8 of 9 patients (89%) achieving measurable residual disease–negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T cells in the blood and 10-fold increases in cerebrospinal fluid CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible, and associated with high rates of durable responses. This trial was registered at www.clinicaltrials.gov as #NCT03233854.

01 Sep 2024·Journal for ImmunoTherapy of Cancer

Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy

Article

Author: Zhu, Hongwen ; Eguchi, Shiori ; Liao, Yanling ; Mardis, Elaine ; Cairo, Mitchell S ; Mo, Xiaokui ; Luo, Wen ; Marcondes, Mario ; Rosenblum, Jeremy M ; Tian, Meijuan ; Ayello, Janet ; Currier, Mark ; Lee, Dean ; Cripe, Timothy ; Miller, Katherine ; Hoang, Hai

Background:

Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due to the immunosuppressive tumor microenvironment (TME). Melanoma cell adhesion molecule (MCAM) is highly expressed on ES and associated with ES metastasis. NKTR-255 is a polymer-conjugated recombinant human interleukin-15 (IL-15) agonist improving NK cell activity and persistence. Magrolimab (MAG) is a CD47 blockade that reactivates the phagocytic activity of macrophages.

Methods:

Transcriptome profiling coupled with CIBERSORT analyses in both ES mouse xenografts and human patient tumors were performed to identify mechanisms of NK resistance in ES TME. A chimeric antigen receptor (CAR) NK cell targeting MCAM was engineered by CAR mRNA electroporation into ex vivo expanded NK cells. In vitro cytotoxicity assays were performed to investigate the efficacy of anti-MCAM-CAR-NK cell alone or combined with NKTR-255 against ES cells. Interferon-γ and perforin levels were measured by ELISA. The effect of MAG on macrophage phagocytosis of ES cells was evaluated by in vitro phagocytosis assays. Cell-based and patient-derived xenograft (PDX)-based xenograft mouse models of ES were used to investigate the antitumor efficacy of CAR-NK alone and combined with NKTR-255 and MAG in vivo.

Results:

We found that NK cell infiltration and activity were negatively regulated by tumor-associated macrophages (TAM) in ES TME. Expression of anti-MCAM CAR significantly and specifically enhanced NK cytotoxic activity against MCAMhighbut not MCAM-knockout ES cells in vitro, and significantly reduced lung metastasis and extended animal survival in vivo. NKTR-255 and MAG significantly enhanced in vitro CAR-NK cytotoxicity and macrophage phagocytic activity against ES cells, respectively. By combining with NKTR-255 and MAG, the anti-MCAM-CAR-NK cell significantly decreased primary tumor growth and prolonged animal survival in both cell- and PDX-based ES xenograft mouse models.

Conclusions:

Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAMhighmalignant metastatic ES.

News (Medical) associated with NKTR-255

12 Mar 2025

·www.prnewswire.com

Nektar Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results

SAN FRANCISCO, March 12, 2025 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today reported financial results for the fourth quarter ended December 31, 2024. Cash and investments in marketable securities on December 31, 2024 were $269.1 million as compared to $329.4 million at December 31, 2023. Nektar's cash and marketable securities are expected to support strategic development activities and operations into the fourth quarter of 2026. "The significant progress we made last year in advancing our immunology pipeline positions us for two value-creating data milestones in 2025," said Howard W. Robin, President and CEO of Nektar. "With enrollment now complete for the atopic dermatitis and alopecia areata Phase 2b trials, we are on track to report topline data for rezpegaldesleukin in the second quarter and in the fourth quarter of this year, respectively. This program is poised to emerge as the first T regulatory cell treatment option to help the millions of patients battling these chronic autoimmune disorders." "We also made progress on our preclinical immunology programs," continued Robin. "We reported the first data for NKTR-0165, our novel antibody targeting TNFR2, and unveiled a new bispecific antibody, NKTR-0166. We plan to submit the IND for NKTR-0165 in the second half of this year." Summary of Financial Results Revenue in the fourth quarter of 2024 was $29.2 million as compared to $23.9 million in the fourth quarter of 2023. Revenue for the year ended December 31, 2024 was $98.4 million as compared to $90.1 million in 2023. Total operating costs and expenses in the fourth quarter of 2024 were $14.8 million as compared to $57.4 million in the fourth quarter of 2023. Total operating costs and expenses for the full year 2024 were $203.6 million as compared to $353.8 million in 2023. Operating costs and expenses for both the fourth quarter and the full year 2024 decreased as compared to 2023 primarily due to a $40.4 million gain from sale of the Huntsville manufacturing facility in 2024, as well as decreases in restructuring and impairment costs. Operating expenses for the full year 2024 also decreased as compared to 2023 due to a one-time $76.5 million non-cash goodwill impairment recognized in the first quarter of 2023. R&D expense in the fourth quarter of 2024 was $28.7 million as compared to $29.9 million for the fourth quarter of 2023. R&D expense for the year ended December 31, 2024 was $120.9 million as compared to $114.2 million in 2023. R&D expense increased for full year 2024 primarily due to increases in development expenses for rezpegaldesleukin partially offset by decreases in employee and related facilities costs, as well as development expenses for NKTR-255. G&A expense was $17.1 million in the fourth quarter of 2024 and $17.3 million in the fourth quarter of 2023. G&A expense for the full year 2024 was $76.8 million as compared to $77.4 million in 2023. G&A expense remained consistent for the full year 2024 as compared to the full year 2023. Decreases in employee costs were offset by a reduction of facilities costs allocated to research and development expense as well as an increase in commercial litigation expense. Restructuring and impairment costs were $1.4 million in the fourth quarter of 2024 and $15.7 million in the full year 2024, as compared to $2.9 million in the fourth quarter of 2023 and $52.0 million in the full year 2023. The full year 2024 amount includes $8.3 million in non-cash lease impairment charges, and $7.4 million in other restructuring costs. The full year 2023 amount includes $7.9 million in severance expense, $35.3 million in non-cash lease impairment charges, and $8.8 million in other restructuring costs. Net income for the fourth quarter of 2024 was $7.3 million or $0.03 basic and diluted earnings per share as compared to a net loss of $42.1 million or $0.22 basic and diluted loss per share in the fourth quarter of 2023. Net loss for the year ended December 31, 2024 was $119.0 million or $0.58 basic and diluted loss per share as compared to a net loss of $276.1 million or $1.45 basic and diluted loss per share in 2023. Excluding the $40.4 million gain from sale of the Huntsville manufacturing facility, and the $1.4 million in non-cash restructuring charges, net loss, on a non-GAAP basis, for the fourth quarter of 2024 was $31.8 million or $0.15 basic and diluted loss per share. Excluding the $40.4 million gain from sale of the Huntsville manufacturing facility, and the $15.7 million in non-cash restructuring and real estate impairment charges, net loss, on a non-GAAP basis, for the full year 2024 was $143.7 million or $0.70 basic and diluted loss per share. 2024 and Recent Business Highlights In February 2025, Nektar announced completion of target enrollment in the REZOLVE-AA 84-patient Phase 2b clinical trial of rezpegaldesleukin in severe-to-very severe alopecia areata. In February 2025, Nektar announced a new clinical trial agreement with TrialNet, an international clinical trial network at the forefront of diabetes research, to evaluate rezpegaldesleukin in a 66-patient Phase 2 study with new onset type 1 diabetes mellitus. In February 2025, the FDA granted Fast Track designation for rezpegaldesleukin for the treatment of adult and pediatric patients 12 years of age and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In January 2025, Nektar announced completion of target enrollment in the REZOLVE-AD 396-patient Phase 2b clinical trial of rezpegaldesleukin in moderate-to-severe atopic dermatitis. At the 66th Annual ASH Meeting in December 2024, Nektar presented proof-of-concept clinical data showing that NKTR-255 following CD19-directed CAR-T therapy enhanced complete response rates in patients with relapsed or refractory large B-cell lymphoma, with 73% of the NKTR-255 treatment group, compared to 50% of the placebo group, achieving a complete response at 6 months. At the 2024 American College of Rheumatology (ACR) Convergence meeting in November 2024, Nektar presented first preclinical data from its novel CSF-1 Program, NKTR-422. The program demonstrated inflammation resolution and tissue repair in multiple preclinical models of chronic inflammatory conditions. At the Society for Immunotherapy of Cancer (SITC) Annual Meeting in November 2024, Nektar and collaborators presented results from a planned interim analysis in the Phase 2 trial of NKTR-255 for the treatment of patients with radiation induced lymphopenia in locally advanced non-small cell lung cancer. These results suggest that NKTR-255 effectively reversed radiation induced lymphopenia in patients with locally advanced NSCLC receiving consolidation therapy with durvalumab. The Phase 2 single-arm study is being conducted by MD Anderson. In November 2024, Nektar announced a definitive agreement with Ampersand Capital Partners to sell its commercial PEGylation manufacturing business in Huntsville, Alabama for $90 million in enterprise value, which is comprised of $70 million in cash and $20 million in equity ownership in the new portfolio company. Nektar and the new Ampersand portfolio company have also entered into manufacturing supply agreements to meet Nektar's PEG reagent needs for rezpegaldesleukin and certain pipeline programs. In October 2024, Nature Communications published results from Phase 1b studies of rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis or chronic plaque psoriasis. Data from both trials demonstrate durable dose-dependent improvements in physician-assessed disease activity and patient-reported outcomes. In the atopic dermatitis study, EASI improvement of ≥75% and vIGA-AD responses were maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders. 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. In October 2024, Nektar announced publication in Blood of Phase 1 data showing that NKTR-255 in Combination with Autologous CD19-22 CAR-T cell therapy in patients with B-cell acute lymphoblastic leukemia exhibited relapse-free/progression-free survival for 67% of patients at 12 months, double that of historical controls. Eight of nine patients achieved complete remission, all without detectable measurable residual disease. At the European Alliance of Associations for Rheumatology (EULAR) in June 2024, Nektar presented preclinical data on NKTR-0165, a TNFR2 agonist antibody, demonstrating selective enhancement of Treg cell function through novel agonistic mechanism. IND-enabling studies are underway for NKTR-0165 with first-in-human studies planned in first half of 2025. Conference Call to Discuss Fourth Quarter 2024 Financial Results Nektar management will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time on March 12, 2025. This press release and live audio-only webcast of the conference call can be accessed through a link that is posted on the Home Page and Investors section of the Nektar website: . The web broadcast of the conference call will be available for replay through April 12, 2025. To access the conference call, please pre-register at Nektar Earnings Call Registration. All registrants will receive dial-in information and a PIN allowing them to access the live call. 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. Nektar's pipeline also includes a preclinical bivalent tumor necrosis factor receptor type II (TNFR2) antibody and bispecific programs, NKTR-0165 and NKTR-0166, and a modified hematopoietic colony stimulating factor (CSF) protein, NKTR-422. 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 Nektar 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," "plan," 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, NKTR-0165, NKTR-0166, NKTR-422, and 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 rezpegaldesleukin, NKTR-0165, NKTR-0166, NKTR-422 and NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin, NKTR-0165, NKTR-0166, NKTR-422 and NKTR-255 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, NKTR-0165, NKTR-0166, NKTR-422 and NKTR-255 are 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) a Fast Track designation does not increase the likelihood that rezpegaldesleukin will receive marketing approval in the United States; (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 November 8, 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. For Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 For Media: Madelin Hawtin LifeSci Communications 603-714-2638 [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

Phase 2Clinical ResultFinancial StatementImmunotherapyPhase 1

10 Feb 2025

·www.prnewswire.com

Nektar Therapeutics Receives Fast Track Designation for Rezpegaldesleukin for the Treatment of Moderate-to-Severe Atopic Dermatitis

SAN FRANCISCO, Feb. 10, 2025 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for rezpegaldesleukin for the treatment of adult and pediatric patients 12 years of age and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Rezpegaldesleukin is an investigational biologic therapy that targets the interleukin-2 receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells (Tregs). In patients with moderate-to-severe atopic dermatitis, rezpegaldesleukin has been shown to rapidly improve measurable exploratory disease outcomes during a 12-week induction treatment phase and for at least 36 weeks after ceasing treatment, demonstrating proof-of-concept in this indication.1 Proof-of-concept efficacy and safety data from a Phase 1b study of rezpegaldesleukin in atopic dermatitis patients were presented at the 2023 EADV Congress in October 2023 (Presentation Link). "We are pleased that rezpegaldesleukin has been designated a Fast Track product," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "Rezpegaldesleukin has the potential to address a significant unmet need for the millions of patients living with moderate-to-severe atopic dermatitis. We remain on track to announce topline data from the induction period of our Phase 2b REZOLVE-AD study in the second quarter of this year. This designation will now allow us to collaborate closely with the agency on the design of the registrational program for rezpegaldesleukin once we've completed Phase 2." The goal of the FDA's Fast Track process is to ensure that important new treatments reach patients as quickly as possible. The designation is granted to investigational therapies that treat serious conditions and have the potential to address an unmet medical need. A drug candidate that receives Fast Track designation is eligible for more frequent meetings and written interactions with the FDA to discuss the drug candidate's development plan as well as possible eligibility for rolling review and priority review. About REZOLVE-AD The REZOLVE-AD (NCT06136741) study enrolled 398 patients with moderate-to-severe atopic dermatitis who had not previously received treatment with biologic or JAK inhibitor therapies. Patients randomized across three different dose regimens of rezpegaldesleukin and placebo for a 16-week induction treatment period. Following this period, patients who meet an Eczema Area and Severity Index (EASI) score threshold for advancement to maintenance are re-randomized to one of two maintenance regimens at their original dose level to receive maintenance therapy either once a month or once every three months. The primary endpoint of the Phase 2b study is mean improvement in EASI score at the end of the 16-week induction treatment period. Secondary endpoints include the proportion of patients achieving Validated Investigator Global Assessment (vIGA-AD) of 0 or 1, those achieving EASI-75, and those achieving a greater than or equal to a 4-point improvement in Itch Numeric Rating Scale (NRS). This trial was initiated in October 2023. Patients were enrolled across approximately 110 sites globally with: 67% enrolled in the European countries of Poland, Bulgaria, Germany, Czechia, Spain, Croatia and Hungary; 17% enrolled in the United States; 11% enrolled in Canada; and 5% enrolled in Australia. Patient randomization was stratified based on baseline disease severity measured by vIGA-AD and geographic region. Enrollment criteria in the study included a minimum EASI score of 16.0, a minimum Body Surface Area (BSA) of 10% and a minimum vIGA-AD of 3 at both screening and randomization. Patients who experienced an unstable course of atopic dermatitis between screening and randomization per investigator assessment were excluded from the study. 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. In addition to the REZOLVE-AD study, it is also being evaluated in the REZOLVE-AA study, a randomized, double blind, placebo-controlled Phase 2b clinical trial for treatment of patients with severe-to-very-severe alopecia areata (NCT06340360). Rezpegaldesleukin is wholly-owned by Nektar Therapeutics. About Atopic Dermatitis Atopic Dermatitis is the most common type of eczema, affecting approximately 30 million people in the United States.2 AD is characterized by a defect in the skin barrier, which allows allergens and other irritants to enter the skin, leading to an immune reaction and inﬂammation. 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. Nektar's pipeline also includes a preclinical bivalent tumor necrosis factor receptor type II (TNFR2) antibody and bispecific programs, NKTR-0165 and NKTR-0166, and a modified hematopoietic colony stimulating factor (CSF) protein, NKTR-422. 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 Nektar on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "will," "announce," "potential," "may," "allow," "can," and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the potential benefits from Fast Track designation, the therapeutic potential of, and future development plans for, rezpegaldesleukin, and the timing for the announcement of rezpegaldesleukin clinical data. 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) a Fast Track designation does not increase the likelihood that rezpegaldesleukin will receive marketing approval in the United States; (ii) 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; (iii) 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); (iv) rezpegaldesleukin is in clinical development, and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (v) 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, 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; (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 November 8, 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. For Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 For Media: Madelin Hawtin LifeSci Communications 603-714-2638 [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

Phase 2Fast TrackPhase 1Clinical ResultImmunotherapy

10 Jan 2025

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Nektar Therapeutics Announces Completion of Target Enrollment in REZOLVE-AD Phase 2b Clinical Trial of Rezpegaldesleukin in Patients with Moderate-to-Severe Atopic Dermatitis

SAN FRANCISCO, Jan. 10, 2025 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the company has completed target enrollment in its REZOLVE-AD Phase 2b study of rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis. Rezpegaldesleukin is a first-in-class interleukin-2 receptor (IL-2R) agonist that proliferates and activates regulatory T cells (Tregs) with promising dose-dependent clinical activity in multiple skin disease settings. Results from multiple clinical trials showed that rezpegaldesleukin safely and dose-dependently increased Tregs and rapidly improved measurable exploratory disease outcomes in patients with moderate-to-severe atopic dermatitis that were largely durable for at least 36 weeks after ceasing treatment, demonstrating proof-of-concept in this indication.1 Proof-of-concept efficacy and safety data from a Phase 1b study of rezpegaldesleukin in atopic dermatitis patients were presented at the 2023 EADV Congress in October 2023 (Presentation Link). "We are pleased to announce that we reached our target enrollment for our 396-patient Phase 2b trial of rezpegaldesleukin," said Howard W. Robin, President and CEO of Nektar Therapeutics. "We are grateful to the patients and physicians whose strong interest in this novel mechanism, together with the proof-of-concept clinical data, led to completing enrollment of the study in just 14 months. Less than 10% of the 30 million atopic dermatitis patients who can receive biologics in the US and Europe are currently receiving treatment and we believe that novel mechanisms are key to helping more patients with this chronic and serious skin disorder. We look forward to announcing the topline data from the 16-week induction treatment period in this study in the second quarter of 2025." The REZOLVE-AD (NCT06136741) study enrolled patients with moderate-to-severe atopic dermatitis who had not previously received treatment with biologic or JAK inhibitor therapies. Patients were randomized across three different dose regimens of rezpegaldesleukin or placebo for a 16-week induction treatment period. Following this period, patients who meet an Eczema Area and Severity Index (EASI) score threshold for advancement to maintenance are re-randomized to one of two maintenance regimens at their original dose level to receive maintenance therapy either once a month or once every three months. The primary endpoint of the Phase 2b study is mean improvement in EASI score at the end of the 16-week induction treatment period. Secondary endpoints include the proportion of patients achieving Validated Investigator Global Assessment (vIGA-AD) of 0 or 1, those achieving EASI-75, and those achieving a greater than or equal to a 4-point improvement in Itch Numeric Rating Scale (NRS). This trial was initiated in October 2023. Patients were enrolled across approximately 110 sites globally with: 67% enrolled in the European countries of Poland, Bulgaria, Germany, Czechia, Spain, Croatia and Hungary; 17% enrolled in the United States; 11% enrolled in Canada; and 5% enrolled in Australia. Patient randomization was stratified based on baseline disease severity measured by vIGA-AD and geographic region. Enrollment criteria in the study included a minimum EASI score of 16.0, a minimum Body Surface Area (BSA) of 10% and a minimum vIGA-AD of 3 at both screening and randomization. Patients who experienced an unstable course of atopic dermatitis between screening and randomization per investigator assessment were excluded from the study. 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. In addition to the REZOLVE-AD study, it is also being evaluated in the REZOLVE-AA study, a randomized, double blind, placebo-controlled Phase 2b clinical trial for treatment of patients with severe-to-very-severe alopecia areata (NCT06340360). Rezpegaldesleukin is wholly-owned by Nektar Therapeutics. About Atopic Dermatitis Atopic Dermatitis is the most common type of eczema, affecting approximately 30 million people in the United States.2 AD is characterized by a defect in the skin barrier, which allows allergens and other irritants to enter the skin, leading to an immune reaction and inﬂammation. 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. Nektar's pipeline also includes a preclinical bivalent tumor necrosis factor receptor type II (TNFR2) antibody and bispecific programs, NKTR-0165 and NKTR-0166, and a modified hematopoietic colony stimulating factor (CSF) protein, NKTR-422. 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 Nektar on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements which can be identified by words such as: "will," "announce," "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, 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 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 November 8, 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. For Investors: Vivian Wu of Nektar Therapeutics 628-895-0661 For Media: Madelin Hawtin LifeSci Communications 603-714-2638 [email protected] Silverberg, J.I., Rosmarin, D., Chovatiya, R. et al. The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials. Nat Commun 15, 9230 (2024). Hanifin, J. M., Reed, M. L. & Eczema Prevalence and Impact Working Group. A population-based survey of eczema prevalence in the United States. Dermatitis 18, 82–91 (2007). 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

Phase 2Clinical ResultPhase 1Immunotherapy

100 Deals associated with NKTR-255

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Indication	Highest Phase	Country/Location	Organization	Date
Mediastinal large B-cell lymphoma	Phase 3	United States	Nektar Therapeutics	23 Dec 2022
Large B-cell lymphoma	Phase 3	United Kingdom	Nektar Therapeutics	30 Jan 2022
Non-Small Cell Lung Cancer	Phase 2	-	Nektar Therapeutics	30 May 2023
Locally Advanced Lung Non-Small Cell Carcinoma	Phase 2	United States	Nektar Therapeutics	10 Jan 2023
Transitional Cell Carcinoma	Phase 2	United States	Nektar Therapeutics	15 Aug 2022
Bladder Cancer	Phase 2	United States	Pfizer Inc.	30 Jan 2022
Bladder Cancer	Phase 2	United Kingdom	Nektar Therapeutics	30 Jan 2022
Bladder Cancer	Phase 2	-	Merck & Co., Inc.	30 Jan 2022
Head and neck cancer metastatic	Phase 2	United Kingdom	Nektar Therapeutics	30 Jan 2022
Metastatic Colorectal Carcinoma	Phase 2	United Kingdom	Nektar Therapeutics	30 Jan 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05664217 (ASH2024) Manual	Phase 2/3	Large B-cell lymphoma Adjuvant	15	NKTR-255	jhkhgjehsj(braytdghcv) = mpbkgjtrms nxqsjwwgtf (tigacznxrz ) View more	Positive	07 Dec 2024
				Placebo	jhkhgjehsj(braytdghcv) = cinkwtltko nxqsjwwgtf (tigacznxrz ) View more
NCT05632809 (RESCUE, SITC2024) Manual	Phase 2	Locally Advanced Lung Non-Small Cell Carcinoma	15	NKTR-255 + durvalumab	jzpexbvffk(ckyahqfyed) = gwtvssioqe tnjqaamjob (iaighbfbnx )	Positive	05 Nov 2024
NCT03233854 (Pubmed) Manual	Phase 1	Refractory B Acute Lymphoblastic Leukemia	11	NKTR-255Anti-CD19/CD22 CAR-T(Stanford University)	qojjecbxud(lhahoewzgg) = None exhrnvyoew (oqaxdamteh )	Positive	05 Jul 2024
				historical controls
NCT04136756 (ASH 12021 \| ASH 22021) Manual	Phase 1	Hematologic Neoplasms	14	NKTR 255	suoepqrsyl(aqzoilrhyl) = qyfhzxyvri uzkcmjnfvw (gevqiciqak ) View more	Positive	05 Nov 2021

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