A Phase 2b, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in the Treatment of Severe to Very Severe Alopecia Areata in Adult Patients (Rezolve AA)

This is an interventional, randomized, double blind, parallel group, placebo-controlled, Phase 2b, 3-arm study to assess the effect of pegylated-recombinant-human interleukin-2 (rezpegaldesleukin) in adult participants with severe to very severe alopecia areata.
The estimated duration includes a screening period of up to 35 days, a 36-week treatment period, an optional 16-week treatment extension period, and a 24-week follow-up period. The maximum study duration is approximately 81 weeks for all participants.

Start Date02 Apr 2024

Sponsor / Collaborator

Nektar Therapeutics

NCT06136741

/ Active, not recruitingPhase 2

A Phase 2b, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in the Treatment of Adult Patients With Moderate-to-Severe Atopic Dermatitis (REZOLVE-AD)

This is an interventional, randomized, parallel group, treatment, Phase IIb, double blind, 4-arm study to assess the effect of pegylated-recombinant-human interleukin-2 (rezpegaldesleukin) in adult participants with moderate to severe atopic dermatitis.
The estimated duration is 15-35 days for screening, an Induction Period of 16 weeks, a Maintenance Period from Week 16-Week 52, and a Posttreatment Follow-Up Period for an additional year up to approximately Week 104 for all patients. Patients with a response at Week 16 (end of induction therapy) will be re-randomized for the maintenance therapy period.

Start Date15 Nov 2023

Sponsor / Collaborator

Nektar Therapeutics

NCT05565729

/ CompletedPhase 1

A Phase 1, Randomized, Placebo-controlled, Participant- and Investigator-blind, Single-dose Study of the Pharmacokinetics of LY3471851 Following Subcutaneous Dosing of LY3471851 in Healthy Participants

The purpose of this study is to compare two different formulations (test & reference) of LY3471851 in healthy participants. This study will compare how much of each formulation gets into the blood stream and how long it takes the body to remove it. Information about any side effects that may occur will also be collected. Participants will remain in the study for about 12 weeks, after receiving the study drug that is LY3471851.

Start Date05 Oct 2022

Sponsor / Collaborator

Nektar Therapeutics

[+1]

100 Clinical Results associated with Rezpegaldesleukin

100 Translational Medicine associated with Rezpegaldesleukin

100 Patents (Medical) associated with Rezpegaldesleukin

Literatures (Medical) associated with Rezpegaldesleukin

01 Jan 2022·Journal of translational autoimmunity

Selective expansion of regulatory T cells by NKTR-358 in healthy volunteers and patients with systemic lupus erythematosus

Article

Author: Furie, Richard ; Levin, Robert ; Diab, Isam ; Fanton, Christie ; Chindalore, Vishala ; Hanan, Nathan ; Zalevsky, Jonathan ; Dickerson, Daniel ; Dixit, Neha ; Haglund, Cat ; Kotzin, Brian L ; Gibbons, Jacqueline

Objective:

To evaluate NKTR-358, a polyethylene glycol-interleukin-2 conjugate composition designed to selectively induce regulatory T cells (Tregs), in first-in-human studies.

Methods:

Healthy volunteers and patients with systemic lupus erythematosus (SLE) received single- or multiple-dose (biweekly) NKTR-358 or placebo in two sequential, randomized, phase 1 studies (single ascending dose [SAD; NCT04133116] and multiple ascending dose [MAD; NCT03556007]). Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics (PK) and immune effects of NKTR-358; exploratory objectives included effects on SLE disease activity.

Results:

There were eight ascending dose cohorts in the SAD study (0.3-28.0 μg/kg: n = 76; placebo: n = 24) and four in the MAD study (3-24.0 μg/kg: n = 36; placebo: n = 12). Most adverse events (AEs) were grade 1-2 injection-site reactions, with no treatment-related serious or severe AEs, or deaths. PK data showed dose proportionality and prolonged exposure (mean half-life: 7.4-12.9 days). Dose-dependent, selective, and sustained increases in percentages and absolute numbers of total CD4⁺ Tregs and CD25^bright Tregs were observed, with no significant changes in conventional CD4⁺ and CD8⁺ T cells, and low-level increases in natural killer cells. At the highest doses tested, administration of NKTR-358 resulted in a 12-17-fold increase in CD25^bright Tregs over baseline that was sustained for 20-30 days.

Conclusion:

NKTR-358 was well tolerated, had a suitable PK profile for biweekly dosing, and led to marked and selective dose-dependent increases in CD25^bright Tregs, with no significant changes in conventional T cells. These results provide strong support for further testing in SLE and other inflammatory diseases.

01 Jan 2021·Journal of translational autoimmunity

NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases

Article

Author: Zhang, Ping ; Dixit, Neha ; Lee, Myong ; Kuo, Peiwen ; Fanton, Christie ; Doberstein, Stephen K ; Cetz, Janet ; Sweeney, Theresa D ; Kamihara, Yusuke ; VanderVeen, Laurie A ; Dixit, Vidula ; Chang, Thomas ; Rubas, Werner ; Langowski, John L ; Kirksey, Yolanda ; Ritz, Jerome ; Tang, Yinyan ; Zalevsky, Jonathan ; Maiti, Mekhala ; Ji, Chunmei ; Kim, Grace ; Kirk, Peter

Impaired interleukin-2 (IL-2) production and regulatory T-cell dysfunction have been implicated as immunological mechanisms central to the pathogenesis of multiple autoimmune and inflammatory diseases. NKTR-358, a novel regulatory T-cell stimulator, is an investigational therapeutic that selectively restores regulatory T-cell homeostasis in these diseases. We investigated NKTR-358's selectivity for regulatory T-cells, receptor-binding properties, ex vivo and in vivo pharmacodynamics, ability to suppress conventional T-cell proliferation in mice and non-human primates, and functional activity in a murine model of systemic lupus erythematosus. In vitro, NKTR-358 demonstrated decreased affinity for IL-2Rα, IL-2Rβ, and IL-2Rαβ compared with recombinant human IL-2 (rhIL-2). A single dose of NKTR-358 in cynomolgus monkeys produced a greater than 15-fold increase in regulatory T-cells, and the increase lasted until day 14, while daily rhIL-2 administration for 5 days only elicited a 3-fold increase, which lasted until day 7. Repeated dosing of NKTR-358 over 6 months in cynomolgus monkeys elicited cyclical, robust increases in regulatory T-cells with no loss in drug activity over the course of treatment. Regulatory T-cells isolated from NKTR-358-treated mice displayed a sustained, higher suppression of conventional T-cell proliferation than regulatory T-cells isolated from vehicle-treated mice. NKTR-358 treatment in a mouse model (MRL/MpJ-Fas^lpr) of systemic lupus erythematosus for 12 weeks maintained elevated regulatory T-cells for the treatment duration and ameliorated disease progression. Together, these results suggest that NKTR-358 has the ability to elicit sustained and preferential proliferation and activation of regulatory T-cells without corresponding effects on conventional T-cells, with improved pharmacokinetics compared with rhIL-2.

01 Sep 2001·Bioconjugate chemistryQ2 · CHEMISTRY

Further Studies on the Site-Specific Protein Modification by Microbial Transglutaminase

Q2 · CHEMISTRY

Article

Author: Sato, Haruya ; Takahara, Yoshiyuki ; Yamada, Naoyuki ; Hayashi, Eiko ; Yatagai, Masanobu

A guinea pig liver transglutaminase (G-TGase)-mediated procedure for the site-specific modification of chimeric proteins was recently reported. Here, an alternative method with advantages over the recent approach is described. This protocol utilizes a microbial transglutaminase (M-TGase) instead of the G-TGase as the catalyst. M-TGase, which has rather broad structural requirements as compared to the G-TGase, tends to catalyze an acyl transfer reaction between the gamma-carboxamide group of a intact protein-bound glutamine residue and various primary amines. To demonstrate the applicability of the M-TGase-catalyzed protein modification in a drug delivery system, we have utilized recombinant human interleukin 2 (rhIL-2) as the target protein and two synthetic alkylamine derivatives of poly(ethyleneglycol) (PEG12; MW 12 kDa) and galactose-terminated triantennary glycosides ((Gal)(3))) as the modifiers. For the M-TGase-catalyzed reaction with PEG12 and (Gal)(3), 1 mol of alkylamine was incorporated per mole of rhIL-2, respectively. Peptide mapping of (Gal)(3)-modified rhIL-2 ((Gal)(3)-rhIL-2) by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) suggested that the Gln74 residue in rhIL-2 was site specifically modified with (Gal)(3). The PEG12-rhIL-2 and (Gal)(3)-rhIL-2 conjugates retained full bioactivity relative to the unmodified rhIL-2. In pharmacokinetic studies, PEG12-rhIL-2 was eliminated more slowly from the circulation than rhIL-2, whereas (Gal)(3)-rhIL-2 accumulated in the liver via hepatic asialoglycoprotein receptor binding. The results of this study expand the applicability of the TGase-catalyzed methodology for the preparation of protein conjugates for clinical use.

News (Medical) associated with Rezpegaldesleukin

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

·www.prnewswire.com

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). 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Indication	Highest Phase	Country/Location	Organization	Date
Alopecia Areata	Phase 2	United States	Nektar Therapeutics	02 Apr 2024
Alopecia Areata	Phase 2	Canada	Nektar Therapeutics	02 Apr 2024
Alopecia Areata	Phase 2	Poland	Nektar Therapeutics	02 Apr 2024
Severe Atopic Dermatitis	Phase 2	United States	Nektar Therapeutics	15 Nov 2023
Severe Atopic Dermatitis	Phase 2	Australia	Nektar Therapeutics	15 Nov 2023
Severe Atopic Dermatitis	Phase 2	Bulgaria	Nektar Therapeutics	15 Nov 2023
Severe Atopic Dermatitis	Phase 2	Canada	Nektar Therapeutics	15 Nov 2023
Severe Atopic Dermatitis	Phase 2	Croatia	Nektar Therapeutics	15 Nov 2023
Severe Atopic Dermatitis	Phase 2	Czechia	Nektar Therapeutics	15 Nov 2023
Severe Atopic Dermatitis	Phase 2	Germany	Nektar Therapeutics	15 Nov 2023

Clinical Result

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Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04433585 (ISLAND-SLE, CTgov)	Phase 2	Systemic Lupus Erythematosus	291	LY3471851 (LY3471851 High Dose)	vjdpnncbzd = osempvpxjv fcskxmuewf (fhbhuskdgw, kuxitrxpdj - nwmltplafq) View more	-	23 Apr 2024
				LY3471851 (LY3471851 Mid Dose)	vjdpnncbzd = zxaiuupnte fcskxmuewf (fhbhuskdgw, jwiqimuzxe - dapshdgixw) View more
NCT04081350 (Phase 1b study, EADV2023)	Phase 1	Dermatitis, Atopic Treg	-	Rezpegaldesleukin 12 µg/kg	htjtanicqn(xtvszjjnwu) = zzqxqkqalh evdleukovv (uokpmquuvi ) View more	Positive	11 Oct 2023
				Rezpegaldesleukin 24 µg/kg	htjtanicqn(xtvszjjnwu) = qbxvzslkjj evdleukovv (uokpmquuvi ) View more
NCT04677179 (INSTRUCT-UC, CTgov)	Phase 2	Colitis, Ulcerative	81	Placebo (Placebo (Induction Treatment Period))	uvdfcfyvdj = svdhfrnmfi tgeywhvwwm (kzfuzdciyn, stonqqohhl - fllkrisots) View more	-	05 Sep 2023
				LY3471851 (Low Dose LY3471851 (Induction Treatment Period))	uvdfcfyvdj = zmymqepiph tgeywhvwwm (kzfuzdciyn, ygjjluvgez - nsxzojtcpb) View more
NCT04433585 (ISLAND-SLE, Corporate Publications) Manual	Phase 2	Systemic Lupus Erythematosus	291	rezpegaldesleukin 300mcg Q2W	gstontuuex(mvfcjpitxe) = twsmunqljq mjxtyckrsj (fkyrfkasek ) View more	Negative	23 Feb 2023
				rezpegaldesleukin 900mcg Q2W	gstontuuex(mvfcjpitxe) = vclaywaizv mjxtyckrsj (fkyrfkasek ) View more
NCT04081350 (Corporate Publications) Manual	Phase 1	Dermatitis, Atopic	43	LY3471851 12 µg/kg	elmcvoeflh(krmmjzdeul) = jsbncnoexn ulwrwimpxv (fvheyumqdk ) View more	Positive	07 Sep 2022
				LY3471851 24 µg/kg	elmcvoeflh(krmmjzdeul) = swrjmsxhtw ulwrwimpxv (fvheyumqdk ) View more
NCT04119557 (Corporate Publications) Manual	Phase 1	Psoriasis	26	LY3471851	wmjjfvcoke(ixcalxxukj) = lggdtnhczs podcllhueg (gcdkfxszvo ) View more	Positive	07 Sep 2022
				Placebo	wmjjfvcoke(ixcalxxukj) = wfcpqwmiyl podcllhueg (gcdkfxszvo ) View more
NCT03556007 (Corporate Publications) Manual	Phase 1	Systemic Lupus Erythematosus	48	NKTR-358	qfmsrjsdcu(uydpayqund) = NKTR-358 was safe and well tolerated in patients with mild-to-moderate SLE lgadvptgyx (ruliibgjqw )	Positive	04 Jun 2020
				Placebo
ACR2019	Not Applicable	Autoimmune Diseases	-	NKTR-358 0.3 µg/kg	eyyvgsmkjc(bhhbzfkjdz) = increased at doses >20 μg/kg hclonyiwdx (fmvaqymucy ) View more	-	10 Nov 2019
				NKTR-358 3.0 µg/kg

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