Benzinga | May 18, 2021 08:05AM EDT

Nektar Therapeutics Highlights First Publication Of Preclinical Data On Anti-Tumor Properties Of IL-15 Agonist In Journal For ImmunoTherapy Of Cancer

-- Results demonstrate NKTR-255's differentiated pharmacologic profile versus precomplexed IL-15 agonists, supporting its potential as a potent immunotherapy agent --

SAN FRANCISCO, May 18, 2021 /PRNewswire/ -- Nektar Therapeutics (NASDAQ:NKTR) today announced the publication of preclinical data from its second major immuno-oncology cytokine program, NKTR-255, in the Journal for ImmunoTherapy of Cancer (JITC). NKTR-255 is a novel recombinant human Interleukin-15 (rhIL-15) receptor agonist designed to activate the IL-15 pathway to expand both natural killer (NK) cells and memory CD8+ T cell populations. The published data demonstrate that NKTR-255 retains the full spectrum of IL-15 biology but with improved pharmacologic properties and anti-tumor activity versus other rhIL-15 agonists. These preclinical findings support Nektar's robust clinical development program for NKTR-255 in patients with hematologic malignancies and solid tumors.



"These findings published today in the Journal for ImmunoTherapy of Cancer demonstrate IL-15's mechanism of action for engaging natural killer cell biology for the treatment of cancers," said Dr. Amita Patnaik, MD, FRCP(C), Co-Director of Clinical Research at the START Center for Cancer Care and a core investigator on the NKTR-255 clinical development program. "NKTR-255 may represent a particularly potent immunotherapeutic, and the data provide a strong rationale for clinical development."

"The findings in JITC describe the foundational science behind NKTR-255 and support its clinical advancement in both liquid and solid tumors," said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. "We look forward to results from our two Phase 1/2 studies designed to evaluate NKTR-255 as a monotherapy as well as in combination with leading antibody-dependent cellular toxicity compounds, rituximab and daratumumab in hematological malignancies, and cetuximab in solid tumors."

Researchers analyzed in vitro pharmacological properties of rhIL-15, NKTR-255 and precomplexed IL-15 cytokines (rhIL-15/IL-15Ra and rhIL-15 N72D/IL-15R? Fc) in receptor binding, cell signaling and cell function assays. In vivo pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the cytokines were evaluated in normal mice, and immunomodulatory effect and anti-tumor activity were assessed in a model of lymphoma.

Key findings are summarized below:

* NKTR-255 maintained a similar receptor binding profile to that of rhIL-15, as compared to precomplexed IL-15 agonists.

* In vivo, NKTR-255 exhibited a PK profile with reduced clearance and a longer half-life (clearance: 2.31 mL/hour/kg; effective half-life: 15.2 hours) relative to rhIL-15 (clearance: 507 mL/hour/kg; effective half-life: 0.168 hours); NKTR-255 also demonstrated prolonged IL-15R engagement in lymphocytes compared with only transient engagement observed for rhIL-15 and precomplexed rhIL-15 N72D/IL-15R? Fc.

* NKTR-255 was shown to provide a more durable and sustained effect on proliferation and activation of NK and CD8+ T cells than precomplexed cytokines.

* The properties of NKTR-255 promoted elevations in functionally competent cytotoxic NK cells in the tumor microenvironment and overall translated into increased survival rates and superior antitumor activity in a B-cell lymphoma model versus the precomplexed cytokines.

NKTR-255 is currently being evaluated in multiple clinical studies in both hematologic malignancies and solid tumors as a monotherapy and in combination with agents that induce antibody-dependent cellular toxicity (ADCC). In the hematological setting, NKTR-255 is being tested in a Phase 1b/2 clinical study as monotherapy and in combination with rituximab or daratumumab in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). It is also being evaluated in a Phase 1b/2 solid tumor trial in combination with cetuximab for the treatment of colorectal cancer (CRC) and head and neck squamous cell carcinoma (HNSCC).

In November 2020, Nektar reported encouraging early data from the NKTR-255 Phase 1/2 study in patients with relapsed/refractory hematologic malignancies at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting. NKTR-255 was administered intravenously (IV) every three weeks (Q3W), a similar dosing to that of checkpoint antibodies. These data indicated that NKTR-255 was biologically active and demonstrated consistent expansion of lymphocytes, with durable and sustained increases in NK and CD8+ T cells in the highly refractory population of patients with MM and NHL. NKTR-255 exhibited a long half-life and was well tolerated with low-grade, cytokine-related AEs that were transient in nature and easily managed. No anti-drug antibodies were reported.