– NKTR-255 Combination Expanded NK Cells and Enhanced ADCC Against Rituximab-Resistant Burkitt Lymphoma (BL) Cells –
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
2023 ASH 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
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.
About
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "will," "could," "develop," "potential," "advance" and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for, NKTR-255. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of NKTR-255 are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) NKTR-255 is an investigational agent and continued research and development for 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) NKTR-255 is in various stages of clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to challenges caused by the COVID-19 pandemic, regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) we may not achieve the expected cost savings we expect from our 2022 corporate restructuring and reorganization plan or our 2023 cost restructuring plan and we may undertake additional restructuring and cost-saving activities in the future, (vi) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vii) certain other important risks and uncertainties set forth in our Annual Report on Form 10-Q filed with the
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