On April 4, 2017 Nektar Therapeutics (Nasdaq: NKTR) reported five preclinical data presentations for its immuno-oncology programs made at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 (Press release, Nektar Therapeutics, APR 4, 2017, View Source [SID1234518459]). The presentations featured new preclinical data on NKTR-214, the Company’s immuno-stimulatory CD122-biased agonist, as well as on NKTR-255, the Company’s IL-15 therapeutic candidate.

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Stephen Doberstein, Ph.D., Nektar’s Senior Vice President and Chief Scientific Officer commented, "The preclinical studies presented at AACR (Free AACR Whitepaper) by both Nektar scientists and our academic collaborators highlight the unique mechanistic profiles of Nektar’s two novel cytokine therapies, NKTR-214 and NKTR-255, including their ability to stimulate multiple cancer-killing CD8+ T cell subtypes within the tumor micro-environment. These data showcase how Nektar’s technology can be leveraged to target the IL-2 and IL-15 pathways in new ways in order to stimulate the body’s immune system to fight cancer."

NKTR-214 is a CD122-biased agonist designed to grow specific cancer-killing T cells and natural killer (NK) cell populations in the body which fight cancer, which are known as endogenous tumor-infiltrating lymphocytes (TILs). NKTR-214 stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these cancer-killing immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. NKTR-214 is currently in Phase 1/2 clinical development.

NKTR-255 is a memory T cell stimulating cytokine designed to engage the IL-15 pathway to induce long-term T cell activation and improve the quality of T cell memory response to treat cancer. Through optimal engagement of the IL-15Rα/IL-2Rγ receptor complex, NKTR-255 stimulates proliferation and survival of CD8+ T cells, natural killer (NK) cells and enhances formation of long-term immunological memory which may lead to sustained anti-tumor immune response.

Details of the five preclinical presentations made at AACR (Free AACR Whitepaper) are as follows:

Presenter: Seema Nagpal, M.D., Stanford University, Department of Neurology
Abstract 1598/Poster 6: "Single agent NKTR-214, an engineered IL2 pathway agonist, localizes in tumor tissue, increases immune infiltrates and prolongs survival in rodent (rattus) glioblastoma (GBM)"
Session: Cytokines: The First Modern Immunotherapies

NKTR-214 single agent provides durable responses as a single agent in an aggressive orthotopic rat brain tumor model.
Treatment of even very large tumors is effective with NKTR-214, prolonging survival in a significant proportion of animals; CD8+ T cells infiltrate into the brain tumors after NKTR-214 therapy.
The marked increase in survival in this aggressive rodent brain tumor model after treatment with single agent NKTR-214 suggests its potential benefit for the treatment of human malignant glioma.
Presenter: Michael J. McNamara, Ph.D., Earle A. Chiles Research Institute, Providence Portland Medical Center
Abstract 1604/Poster 12: "NKTR-214 Synergizes with Radiotherapy to Drive Tumor Regression"
Session: Cytokines: The First Modern Immunotherapies

NKTR-214 combines positively with radiation therapy which is a standard of care for multiple tumor types and is a readily available therapy.
Gene expression patterns reveal a strong T cell activation signature including up-regulation of tumor-killing granzymes and perforins.
Combined therapy increased the frequency of tumor-reactive CD8 T cells in the target (irradiated) tumors as measured by increased TCR ligation (Nur77-GFP+) and AH1-A5 tetramer staining.
Presenter: Giulia Parisi, Ph.D., Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA)
Abstract 2671/Poster 30: "Antitumor activity of NKTR-214 in combination with Adopted Cell Transfer (ACT) in an aggressive murine melanoma"
Session: Immune Response to Hematopoietic Tumors: New Development in Tumor Immunology

NKTR-214 improves the antitumor activity of adoptive cellular therapy in an aggressive murine melanoma model.
Treatment with NKTR-214 + ACT robustly mobilizes T cells into the tumor where they durably persist.
The robust and long-lasting effect of NKTR-214 supports its potential use in combination with cell-based therapeutics.
Presenter: Samira Khalili, Ph.D., Nektar Therapeutics
Abstract 1617/Poster 25: "Mechanistic modeling of the pharmacokinetics, pharmacodynamics and receptor pharmacology of NKTR-214: A kinetically-controlled CD122 agonist for cancer immunotherapy"
Session: Cytokines: The First Modern Immunotherapies

NKTR-214 significantly favors occupancy at IL-2 receptor βγ compared to the IL-2 receptor αβγ.
NKTR-214 delivers a controlled, sustained, and biased signal through the IL-2 receptor complex.
Presenter: Peiwen Kuo, Ph.D., Nektar Therapeutics
Abstract 1603/Poster 11: "NKTR-255 engages the IL-15 pathway driving CD8 T cell survival and CD8 memory T cell proliferation"
Session: Cytokines: The First Modern Immunotherapies

NKTR-255 induces multiple memory CD8+ T cell subtypes, including effector, central and stem memory populations.
Single dose NKTR-255 results in sustained IL-15-mediated activity not achievable with conventional IL-15.
NKTR-255 has single agent ef­ficacy in the CT-26 lung metastatic model, demonstrating signifi­cant lung nodule inhibition.