avipendekin pegol (NKTR-255) / Nektar Therap - LARVOL DELTA

Summary of Financial Results (PRNewswire) - "R&D expense in the third quarter of 2025 was $27.3 million as compared to $35.0 million for the third quarter of 2024....R&D expense decreased in the first nine months of 2025 primarily due to a decrease in expense for the development of NKTR-255, partially offset by an increase in expenses for the development of rezpegaldesleukin and NKTR-0165."

Commercial • Atopic Dermatitis • Immunology • Oncology

Combination IL-1RAP-Targeted Chimeric Antigen Receptor Natural Killer Cell Therapy and Adjuvant Immunomodulation to treat Acute Myeloid Leukemia (SITC 2025) - "NK cells secreted significantly higher levels of Granzyme B, IFNγ, and perforin compared to unmodified NK cells, and their secretions were further significantly augmented by NKTR-255 or cam161533 (figure 1C).Conclusions IL-1RAP.CAR NK cells, in combination with IL-15- based immunomodulation, exhibited potent in vitro anti-AML cytotoxicity. These results support further evaluation of this combinatorial approach in human AML xenograft models.Acknowledgements Supported by DOD HT94252410682"

Clinical • Immunomodulating • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • GZMB • IFNG • IL15 • IL1RAP

Enhanced Cytotoxicity of Anti-ROR1 CAR NK Cells Against Glioblastoma via Combined Treatment with Oncolytic Virus and NKTR-255 (SITC 2025) - "Our group has successfully ex vivo expanded functional peripheral blood NK cells (exPBNK) and electroporated with anti-ROR1 CAR mRNA.3 Oncolytic herpes simplex viruses C134, a neurovirulent deleting γ134.5 and expressing the human cytomegalovirus IRS1, is a promising experimental therapy.4 We previously demonstrated enhanced cytotoxicity against neuroblastoma using HSV expressing human IL-21(HSV C021) in combination with ROR1.CAR.5 NKTR-255 is an investigational IL-15Rα-dependent, polymer-conjugated IL-15 agonist that promotes NK cell expansion. Increased IFNγ secretion was also confirmed by ELISA assay (p < 0.05) (figure 1C).Conclusions The combination of HSV C021 with NKTR-255 significantly enhanced ROR1.CAR cytotoxicity against GBM in vitro, accompanied by elevated IFNγ secretion. In vivo evaluation using humanized NSG models is currently underway."

IO biomarker • Oncolytic virus • Brain Cancer • Glioblastoma • Neuroblastoma • Oncology • Solid Tumor • GZMB • IFNG • IL15 • IL21 • ROR1

Synergistic anti-leukemic effect of NKTR-255 and TGFβ-imprinted CD33.CAR natural killer cells (SITC 2025) - "Notably, this combination also significantly rescued the declining cytotoxicity of NK TGFβi alone, rendering a cytotoxicity of 83.8 ± 0.9% at cycle 4, vs 58.2 ± 7.2% for NK + NKTR-255, and 40.7 ± 4.7% for NK TGFβi (p<0.01), suggesting synergism of TGFβ imprinting and NKTR-255 (figure 1A, B).Consistently, flow cytometry demonstrated higher NK persistence and fewer AML cells in TGFβi and NKTR-255 modified conditions at cycle 5 (figure 1C). The improved NK survival correlated with an increase in pSTAT5 and CD25 in TGFβi NK at cycle 1 (figure 1D).Conclusions TGFβ imprinting and NKTR-255 synergistically enhanced and sustained anti-AML activity of NK and CD33.CAR NK cells, supporting a novel strategy to improve NK-based immunotherapy for AML.Acknowledgements Supported by DOD W81XWH-21-1-0841."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • IFNG • IL15 • IL2RA • TGFB1 • TGFBI

Targeting Osteosarcoma by ex-vivo Expanded NK Cells in Combination with IL-15 Agonist and Anti-GD2 antibody (SITC 2025) - "Baldrick's Foundation, Pediatric Cancer Research Foundation, Children's Cancer Fund. We thank Nektar Therapeutics for generously providing NKTR-255.Ethics Approval All animal experiments were approved by the Institutional Animal Care and Use Committee at New York Medical College (Protocol #15112) and performed in accordance with the ethical standards of the institutional research committee.Abstract 310 Figure 1Request permissionsExpanded NK cells combined with dinutuximab and NKTR-255 significantly enhanced NK cytotoxicity in vitro (A and B), decreased tumor growth (C) and improved animal survival (D) in OS xenograft mouse model"

Combination therapy • Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CD8 • IFNG • IL15 • IL2

CXCL10-induced chemotaxis of ex vivo-expanded natural killer cells combined with NKTR-255 enhances anti-tumor efficacy in osteosarcoma. (PubMed, Mol Ther Oncol) - "Single-cell RNA sequencing and mass cytometry revealed upregulated apoptosis and transforming growth factor-β (TGF-β) signaling as the potential mechanisms of response/resistance to NK cell therapy in vivo. Our findings highlight potential application of chemokine-enhanced NK tumor infiltration in combination with an IL-15 agonist as a novel approach to effective treatment of OSA."

Journal • Preclinical • Hematological Disorders • Hematological Malignancies • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • CXCL10 • CXCL9 • CXCR3 • IL15 • TGFB1

NCI-2022-02316: NKTR-255 in Combination With CAR-T Cell Therapy for the Treatment of Relapsed or Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Fred Hutchinson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • CD19

NKTR-255 Enhances Complete Response Following CD19 CAR-T in Patients with Relapsed/Refractory Large B-cell Lymphoma. (PubMed, Blood Adv) - P2/3 | "In this phase 2, randomized, double-blind, placebo-controlled, multicenter study of NKTR-255 versus placebo following CD19 CAR T-cell therapy, eligible patients with R/R LBCL were treated with one of two FDA-approved CAR T-cell products, axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel). NKTR-255 was well-tolerated, safe, and augmented CR6 for LBCL patients. Based on the findings, additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR T-cell, including other cellular therapies, are warranted (ClinicalTrials.gov number NCT05664217)."

Clinical • Journal • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD8

ENHANCED CAR T-CELL EXPANSION AND DURABLE COMPLETE RESPONSES WITH NKTR-255 PLUS LISOCABTAGENE MARALEUCEL IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (ICML 2025) - P1 | "The combination of NKTR-255 and liso-cel in R/R LBCL was well tolerated and safe. Higher CAR-T expansion and AUC0–28 were observed in pts treated with the OBR compared to liso-cel alone. CRs appear to be durable, with only 1 relapse."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8 • IL15

ENHANCED CAR T-CELL EXPANSION AND DURABLE COMPLETE RESPONSES WITH NKTR-255 PLUS LISOCABTAGENE MARALEUCEL IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (EHA 2025) - P1 | "The combination of NKTR-255 and liso-cel in R/R LBCL was well tolerated and safe. Higher CAR T-cell expansion and AUC0-28 were observed in pts treated with the OBR compared to liso-cel alone. CRs appear to be durable, with only one relapse."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8 • IL15

Combinational Natural Killer Cell- Based Therapies Treating Rituximab- Resistant Burkitt Lymphoma (ASPHO 2025) - "Obinutuzumab (OB) is a glycoengineered humanized type-II mAb recognizing a unique CD20 epitope with significantly enhanced antibody-dependent cellular cytotoxicity than rituximab. Our results demonstrated the efficacy of combinatorial NK immunotherapy in treating rituximab-resistant BL cells. Our future studies will determine the in vivo efficacy of NK in combination with cam161519 and OB, and CD20.CAR NK in combination with cam161519 or NKTR-255 in resistant BL models."

Burkitt Lymphoma • Hematological Malignancies • Lymphoma • Oncology • IFNG • IL15

Combinational Targeted Chimeric Antigen Receptor NK Cell Therapy to Treat Acute Myeloid Leukemia (ASPHO 2025) - "We hypothesize that anti-CD123 chimeric antigen receptor NK (CD123.CAR NK) cells, combined with adjuvant IL15 Trispecific Killer Engager (TriKE) recognizing CD16 on NK cells and CD33 on AML cells (cam161533), or polymer conjugated IL-15 (NKTR-255), will significantly enhance the anti-tumor activities of NK cells... Combinatorial CD123.CAR NK and adjuvant IL-15 based immunomodulation had significant in vitro anti-AML cytotoxicity. We will investigate the anti-AML effect of the combination utilizing human AML xenografts."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • CD123 • CD33 • CD34 • GZMB • IL15 • IL3RA

A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley) (clinicaltrials.gov) - P2 | N=256 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2025 ➔ Jul 2026 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

Chemokine engineering significantly enhanced migration and tumor infiltration of ex vivo-expanded natural killer cells in osteosarcoma (AACR 2025) - "To evaluate NK cell tumor infiltration, we injected human NK cells with an IL-15 agonist, NKTR-255, and harvested and dissociated tumors 5-7 days after NK injection for flow cytometry analysis...Our in vitro and in vivo data demonstrated that secretion of CXCL9, -10, and -11 from OS significantly enhanced NK migration and NK infiltration into the OS TME. We are actively investigating the in vivo anti-tumor efficacy of expanded NK cells against CXCL9, -10, or -11-secreting disseminated OS tumors."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCL9 • CXCR3 • IL15 • IL2 • PTPRC

NKTR-255 Plus Anti-CD19 CAR T-Cell Therapy Demonstrates Safety and Preliminary Efficacy in R/R LBCL (OncLive) - P2/3 | N=15 | NCT05664217 | Sponsor: Nektar Therapeutics | "In the intent-to-treat (ITT) population, the 6-month CR rate was 73% among patients who received NKTR-255 at any dose level (n = 11) vs 50% among those who received placebo (n = 4). The 6-month CR rates among efficacy-evaluable patients in the NKTR-255 (n = 10) and placebo (n = 4) arms were 80% and 50%, respectively. Among patients in the ITT population who received NKTR-255 at dose levels of 1.5 mcg/kg (n = 5), 3.0 mcg/kg (n = 3), and alternating 3.0 mcg/kg and 6.0 mcg/kg (n = 3), the 6-month CR rates were 80%, 67%, and 67%, respectively. The 6-month CR rates among efficacy-evaluable patients in these respective populations were 100% (n = 4/4), 67% (n = 2/3), and 67% (n = 2/3), respectively."

P2/3 data • Diffuse Large B Cell Lymphoma • Large B Cell Lymphoma

NKTR-255 vs Placebo Following CD19-directed CAR-T Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P2/3 | N=15 | Terminated | Sponsor: Nektar Therapeutics | N=400 ➔ 15 | Trial completion date: Jan 2029 ➔ Aug 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ May 2024; Sponsor decided to end the study

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

NCI-2022-02316: NKTR-255 in Combination With CAR-T Cell Therapy for the Treatment of Relapsed or Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • CD19

Combinatorial Immunotherapy of Mcam Targeting Chimeric Antigen Receptor Modified Expanded Natural Killer Cells and IL-15 Agonist Against Neuroblastoma (TCT-ASTCT-CIBMTR 2025) - "Combination with NKTR-255 further enhanced the anti-tumor effects of CAR NK cells (p < 0.001 compared to vehicle control, p < 0.05 compared to CAR NK), and further prolonged animal survival (100% vs 30% survival at day 126 compared to CAR NK, p < 0.05) (Fig 1D, E). Conclusions Our 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."

IO biomarker • CNS Tumor • Melanoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • IFNG • IL15 • IL2 • MCAM • NKG2D

Targeting Ewing Sarcoma By IL1RAP CAR Modified Ex-Vivo Expanded TGFβ Imprinted NK Cells in Combination with IL-15 Agonist and Anti-GD2 Antibody (TCT-ASTCT-CIBMTR 2025) - "Conclusions Our data demonstrated enhanced anti-tumor efficacy of IL1RAP CAR NK/TGFβi-NK cells alone and combined with NKTR-255 and dinutuximab against ES in vitro and in vivo. These CAR engineered TGFβi NK cells in combination with NK function and persistence enhancing immune modulators constitute potential novel effective immunotherapies for patients with high-risk ES."

Combination therapy • IO biomarker • Preclinical • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • IFNG • IL15 • IL1RAP • TGFB1 • TGFBI

NKTR-255 Vs Placebo to Enhance Complete Responses and Durability Following CD19-Directed CAR-T Therapy in Patients with Relapsed/ Refractory (R/R) Large B-Cell Lymphoma (LBCL) (TCT-ASTCT-CIBMTR 2025) - P1, P2/3 | "15 patients with LBCL were randomized between Mar and Dec 2023. All patients received CD19-CAR-T cell therapy and ≥1 dose of study treatment; 12/15 (80%) received axi-cel and 3/15 (20%) received liso-cel. In total, 11 were randomized to the NKTR-255 (5 at 1.5 µg/kg; 3 at 3 µg/kg; 3 at 3 µg/kg then 6 µg/kg cycle 2+) and 4 were randomized to placebo."

Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8 • IL15

A Phase 1 Clinical Trial of NKTR-255 With CD19-22 CAR T-Cell Therapy for Refractory B-Cell Acute Lymphoblastic Leukemia (Cancer Network) - P1 | N=56 | NCT03233854 | "Researchers at Stanford University have conducted a phase 1 clinical trial (NCT03233854) evaluating the combination of a bispecific chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and CD22 (CAR19-22) with NKTR-255...The study enrolled 11 patients, 9 of whom received CAR19-22 followed by NKTR-255. The combination therapy was well-tolerated, with no dose-limiting toxicities. Transient fever and myelosuppression were the most common adverse events. Remarkably, 8 of the 9 patients (89%) achieved measurable residual disease-negative remission, with progression-free survival at 12 months reaching 67%, nearly double the rate of historical controls (38%). These results suggest that combining CAR19-22 with NKTR-255 may significantly improve the durability of remission in B-ALL patients."

P1 data • Acute Lymphocytic Leukemia

NKTR-255 Vs Placebo to Enhance Complete Responses and Durability Following CD19-Directed CAR-T Therapy in Patients with Relapsed/ Refractory (R/R) Large B-Cell Lymphoma (LBCL) (ASH 2024) - P1, P2/3 | "Eligible patients with R/R LBCL were treated with one of two FDA-approved CAR-T products (axicabtagene ciloleucel or lisocabtagene maraleucel). Conclusions : Preliminary data from the randomized, double-blind, placebo-controlled study showed NKTR-255 adjuvant to CD19 CAR-T cell therapy in LBCL was well-tolerated, safe and efficacious to enhance the CR rate of CD19 CAR-T cell therapy alone at month 6. Additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR-T therapy and other cellular therapies are warranted."

Clinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD8 • IL15

Nektar Therapeutics Announces NKTR-255 Following CD19-directed CAR-T Therapy Enhanced Complete Response Rates in Patients with Relapsed or Refractory Large B-cell Lymphoma at the 66th Annual ASH Meeting (PRNewswire) - P2/3 | N=400 | NCT05664217 | Sponsor: Nektar Therapeutics | "In this multicenter, double-blind Phase 2 study, patients were randomized to receive one of three dose regimens of NKTR-255 or placebo intravenously starting 14 days after CAR-T infusion. In the fifteen-person clinical trial, the NKTR-255 combined treatment group demonstrated an improved CRR at six months, achieving 73% compared to 50% for the placebo....Additionally, two patients treated with NKTR-255 converted from stable disease or partial response to complete responses at six months. No conversions from stable disease or partial response to complete response were observed in the placebo arm of the trial....The reported clinical benefit surpasses the published historical benchmark data from multiple pivotal trials and real-world meta-analyses of currently available commercial CD19 CAR-T cell therapies, which demonstrate 6-month complete response rates of 41% to 44%."

P2 data • Diffuse Large B Cell Lymphoma

REStoring lymphoCytes using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): preplanned interim safety and efficacy analysis (SITC 2024) - P2 | "Methods NKTR-255 (3µg/kg) is given after CRT (day 0), with repeat doses given every 4 weeks concurrently with durvalumab up to 1 year. Ethics Approval All patients are consented to an institutional review board approved clinical trial protocol.Download figure Open in new tab Download powerpoint Abstract 1489 Figure 1 Trial schema. Schema to show eligibility and workflow of the trial"

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

Combinatorial immunotherapy of anti-MCAM CAR-modified expanded natural killer cells and NKTR-255 against neuroblastoma. (PubMed, Mol Ther Oncol) - "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 MCAMhigh malignant NB."

IO biomarker • Journal • CNS Tumor • Melanoma • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • IL15 • MCAM