Nektar Therapeutics Announces Pre-clinical Data On NKTR-214

(RTTNews) - Nektar Therapeutics (NKTR) announced new preclinical data for the company's investigational immuno-stimulatory cytokine therapy, NKTR-214, which demonstrate both its activity as a single-agent and its synergistic activity with checkpoint blockade.

In a TCR repertoire analysis conducted to assess both anti-tumor T cell clonality and T cell tumor infiltration (TIL clonality and infiltration), the combination of NKTR-214 and a checkpoint inhibitor resulted in dramatically higher increases for both parameters as compared to dual checkpoint inhibition.

TIL clonality establishes the frequency of T cells with a specific TCR Vß and TCR Jß chain usage at the tumor site, which suggests increased CD8-positive effector T cell function against the specific tumor. The concomitant presence of both TIL clonality and infiltration has been significantly correlated with clinical response and better survival outcomes in patients.1 In a CT26 colon carcinoma model, sequencing for TCRs in the tumor was conducted using Adaptive Biotechnologies' ImmunoSEQ platform.

Measurements of TIL clonality and infiltration were assessed seven days after treatment. NKTR-214 as a single-agent led to superior increases in TIL clonality and infiltration as compared to either anti-CTLA-4 or anti-PD-1 therapy alone. The combination of NKTR-214 with either mode of checkpoint inhibition led to superior increases in both TIL clonality and infiltration relative to the combination of CTLA-4 and PD-1 inhibitors. The highest increases occurred when NKTR-214 was added to an anti-PD-1 therapy.

NKTR-214 is an investigational CD122-biased agonist currently in Phase 1/2 clinical development. NKTR-214 is designed to stimulate the patient's own immune system to kill tumor cells by preferentially activating production of specific immune cells which promote tumor killing, including CD8-positive T cells and Natural Killer (NK) cells, within the tumor micro-environment. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these types of T cells.