On August 16, 2022 Nektar Therapeutics (Nasdaq: NKTR) reported the publication of preclinical data in Blood Advances, the open-access journal of the American Society of Hematology (ASH) (Free ASH Whitepaper), highlighting the effects of NKTR-255, a novel polymer-conjugated human IL-15, on natural killer (NK) cell function and proliferation in multiple myeloma (MM) (Press release, Nektar Therapeutics, AUG 16, 2022, View Source [SID1234618438]).

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"These findings published today in Blood Advances demonstrate the promising anti-tumor activity of IL-15 in engaging natural killer cell biology in indications with immunosuppressive tumor microenvironments as in multiple myeloma," said Nikhil C. Munshi, MD, Professor of Medicine at Harvard Medical School, Director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. "Among other immune cells, the NK cell expansion and improved function induced by NKTR-255 is contributing to more effective control of multiple myeloma tumor growth, raising a potential scope for synergism with other anti-MM therapies such as anti-CD38 antibodies."

The Dana-Farber team analyzed in vitro pharmacological properties of NKTR-255 in engaging the IL-15 pathway and stimulating NK cells against MM cells. The research also looked at the anti-tumor activity of combining NKTR-255 with the anti-CD38 antibody, daratumumab, in vitro and in vivo.

"The published data demonstrate that NKTR-255 not only enhances antitumor responses of human NK cells against MM target cells, but also increases ex vivo expression of NK activating receptors and adhesion molecules. Furthermore, studies in a humanized MM mouse model show that NKTR-255 enhances in vitro antibody-dependent cellular cytotoxicity (ADCC) of NK cells and synergizes with daratumumab to reduce MM cell growth," said Mariateresa Fulciniti, Ph.D., the senior author on this manuscript at Dana-Farber. These preclinical findings support Nektar’s robust clinical development program for NKTR-255 and further evaluation of the novel immunotherapeutic approach in MM, alone or in combination with monoclonal antibodies or potentially with other immunomodulatory drugs.

Key findings are summarized below:

NKTR-255 enhances antitumor responses of myeloma derived human NK cells against MM target cells.
NKTR-255 enhances in vitro ADCC of NK cells and synergizes with daratumumab to reduce MM growth in humanized mouse model.
NKTR-255 increases ex vivo expression of NK activating receptors and adhesion molecules.
Augmenting NK cell number and functions shows effectiveness against MM cells in the context of their bone marrow milieu.
The full citation of this article can be accessed here.

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.

Preclinical findings suggest NKTR-255 has the potential to synergistically combine with antibody-dependent cellular cytotoxicity molecules as well as to enhance CAR-T therapies. Nektar has initiated a Phase 1 dose escalation and expansion clinical study of NKTR-255 in adults with relapsed or refractory non-Hodgkin lymphoma or multiple myeloma, as well as a Phase 1/2 clinical study of NKTR-255 in patients with relapsed or refractory head and neck squamous cell carcinoma or colorectal cancer. Nektar is also continuing its oncology clinical collaboration with Merck KGaA and Pfizer Inc. to evaluate the maintenance regimen of NKTR-255 in combination with avelumab, a PD-L1 inhibitor, in patients with locally advanced or metastatic urothelial carcinoma in the Phase II JAVELIN Bladder Medley study. Nektar is also currently designing a Nektar- sponsored Phase II study combining NKTR-255 with approved CAR-T cell therapies in diffuse large B-cell lymphoma, which it aims to initiate in the first quarter of 2023.