On December 11, 2023 Nektar Therapeutics (NASDAQ:NKTR) reported that collaborators from the Cairo Laboratory at New York Medical College presented a poster highlighting new preclinical data on NKTR-255 at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrating that NKTR-255 significantly enhanced the cytotoxicity of expanded Natural Killer (NK) cells when combined with obinutuzumab against rituximab-resistant BL cells and significantly improved the survival of mice xenografted with Raji-4RH compared to controls (Press release, Nektar Therapeutics, DEC 11, 2023, View Source [SID1234638452]).

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NKTR-255 is a novel polymer-conjugated human IL-15 receptor agonist currently being studied in three separate clinical studies in combination with cell therapies and immunotherapies. Preclinical and early clinical data suggest that NKTR-255 can improve proliferation and persistence of NK and CD8+ T cells to enhance specific anti-tumor activity.

"Both in vitro and in vivo data show the promising synergistic potential of combining NKTR-255 with an anti-CD20 antibody, obinutuzumab, in enhancing anti-tumor immune response, particularly in an aggressive tumor model like Burkitt lymphoma," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "Results like these confirm our belief that NKTR-255 could become a valuable addition to current standard of care across multiple oncology indications, particularly in hematologic malignancies."

2023 ASH (Free ASH Whitepaper) presentations are available for download at www.nektar.com/science/scientific-posters-and-presentations.

Key details and takeaways from the presentation are as follows:

Abstract 2063: "Optimizing Ex-Vivo Expanded NK Cell- Mediated Cellular Cytotoxicity By Obinutuzumab Combined with NKTR-255 in Burkitt Lymphoma (BL)", Chu YY, et al.

NKTR-255 significantly promoted NK cell proliferation, and significantly enhanced the antibody-dependent cellular cytotoxicity (ADCC) of expanded NK cells when combined with obinutuzumab against rituximab-resistant BL cells in vitro.
NKTR-255 significantly enhanced the release of interferon-gamma (IFNγ) and granzyme B, proinflammatory cytokines with multiple functions including enhancing anti-tumor immune response, by NK cells when combined with obinutuzumab against BL cells in vitro.
NKTR-255 combined with obinutuzumab and NK cells significantly extended survival, compared to NK cells alone, in humanized rituximab-resistant BL cells xenografted mouse models.
About NKTR-255

NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body’s innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response.

NKTR-255 is currently being studied in three separate clinical studies in combination with cell therapies and immunotherapy. A Phase 2/3 study is underway that combines NKTR-255 with approved CAR-T cell therapies in patients with diffuse large B-cell lymphoma, which is currently recruiting (NCT05664217). NKTR-255 is also being studied in a Phase 2 study in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma in the Merck KGaA-sponsored JAVELIN Bladder Medley trial (NCT05327530). In September, the company announced a new clinical collaboration whereby CBMG will be adding NKTR-255 to its ongoing CBMG-sponsored Phase 1 clinical trial evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer, which is being conducted at Duke Cancer Institute (NCT05676749).

In addition, there are two ongoing investigator sponsored trials (ISTs) evaluating NKTR-255 as adjunct therapy following a CAR-T cell therapy and one study evaluating NKTR-255 in combination with PD-1 immunotherapy. Fred Hutchinson Cancer Center is conducting a Phase 1 study evaluating NKTR-255 following lisocabtagene maraleucel treatment in patients with relapsed/refractory large B-cell lymphoma (NCT05359211), and Stanford University is conducting a Phase 1 study evaluating NKTR-255 following an investigational CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (NCT03233854). M.D. Anderson Cancer Center is conducting a Phase 1 study evaluating NKTR-255 in combination with durvalumab in patients with locally advanced NSCLC (NCT05632809).