On April 24, 2018 Nektar Therapeutics (NASDAQ:NKTR) reported that it has entered into a new clinical collaboration with Takeda Pharmaceutical Company Limited to evaluate Nektar’s investigational medicine, NKTR-214, with Takeda’s investigational medicine, TAK-659, as a potential combination treatment regimen in multiple cancer settings (Press release, Nektar Therapeutics, 24 24, 2018, View Source [SID1234525633]). NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. TAK-659 is a dual inhibitor of both spleen tyrosine kinase (SYK), a kinase involved in cell proliferation and FLT-3, a cytokine receptor in the receptor tyrosine kinase class III.
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"We look forward to collaborating with Takeda to explore a range of combination therapy approaches with NKTR-214 and TAK-659 in liquid and solid tumor settings," said Jonathan Zalevsky, PhD, Chief Scientific Officer and Senior Vice President of Research, Nektar. "Importantly, this clinical collaboration will allow us to understand how we can increase the clinical benefit of immunotherapies for patients when we leverage multiple I-O modalities and target the immune cycle in complementary and novel ways."
Under the terms of the collaboration, Nektar and Takeda will each maintain global commercial rights to their respective investigational medicines. Nektar and Takeda will split the costs related to the clinical trial and each company will contribute their respective compounds to the clinical collaboration. The first trial is expected to start in the second half of 2018 and will evaluate the combination of an every three-week schedule of NKTR-214 with oral daily doses of TAK-659 in patients with Non-Hodgkin Lymphoma.
"Based upon highly compelling preclinical data, we are looking forward to combining Nektar’s unique CD122-biased agonist with TAK-659, which is a dual inhibitor of both SYK and FLT-3," said Phil Rowlands, PhD, Head, Oncology Therapeutic Area Unit, Takeda. "NKTR-214 is unique in that it can stimulate tumor-killing T-cells in the tumor micro-environment itself. By combining with TAK-659, we hope to target different stages of the cancer immunity cycle in a combination regimen. This collaboration is aimed at achieving our goal of allowing more patients with different types of cancer to benefit from immunotherapies."
NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting CD8+ effector T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. NKTR-214 targets CD122 specific receptors found on the surface of these cancer-fighting immune cells in order to stimulate their proliferation. NKTR-214 is being evaluated in multiple clinical trials in cancer patients. It has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.
TAK-659 is an orally-available investigational reversible dual SYK/FLT-3 inhibitor. SYK is a non-receptor cytoplasmic kinase that binds to phosphorylated immuno-receptor tyrosine-based activating motifs and mediates cellular proliferation and survival. Mutations in FLT-3 genes can result in the constitutive activation of the FLT-3 receptor and result in acute myeloid leukemia and acute lymphoblastic leukemia. TAK-659 demonstrates both direct- and immune-mediated tumor cell kill mechanisms. It is currently being explored in clinical studies as a single agent and in combination in solid and hematological malignancies