Date: 2017-07-10
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at 13th World Congress of Inflammation in London
Company: Nektar Therapeutics (USA - CA)
Product: NKTR-358
Action
mechanism:
- immunotherapy product. NKTR-358 works by optimally targeting the interleukin-2 receptor complex in order to stimulate proliferation and activation of regulatory T cells. By increasing the number of regulatory T cells, the pathogenic auto-reactive T cells can be controlled and the proper balance of effector and regulatory T cells can be achieved to restore the body's self-tolerance mechanisms.
- In preclinical studies, NKTR-358 has demonstrated that it could suppress antigen-driven inflammation in a model of cutaneous hypersensitivity. NKTR-358 has also shown that it reduces markers of progression in a mouse model of systemic lupus erythematosus.
- NKTR-358 is being developed as a once or twice-monthly self-administered injection for a number of auto-immune diseases.
Disease:
Therapeutic
area: Autoimmune diseases – Inflammatory diseases
Country:
Trial
details:
Latest
news:
- • On July 10, 2017, Nektar Therapeutics announced positive preclinical results for NKTR-358, a first-in-class resolution therapeutic for autoimmune disease. The new preclinical data demonstrate that treatment with NKTR-358 induces profound regulatory T cell effects and suppresses inflammation in multiple preclinical models. The data were highlighted in an oral presentation at the 13th Annual World Congress on Inflammation on July 9, 2017.
- In preclinical studies, NKTR-358 demonstrates attenuated and optimized affinity for human IL-2 receptors to promote biological activity favoring activation of regulatory T cells over conventional T cells. This preferential activity combined with prolonged exposure in vivo led to significant Treg mobilization in blood and spleen following a single subcutaneous administration in rodents. Increases in regulatory T cells were sustained for 7 to 10 days, and were concomitant with increases in cytometric markers of activation and increased suppressive capacity.
- In non-human primates, a single administration of NKTR-358 led to increases in Treg mobilization and activity sustained for over 14 days, a response greatly superior in magnitude, duration and specificity compared to an equivalent total dose of rhIL-2 administered daily for five days. In a mouse model of cutaneous hypersensitivity, NKTR-358 administration significantly suppressed antigen-induced inflammatory responses, an effect which was antigen-specific and associated with establishment of Treg memory. Similar results were achieved in analogous model using non-human primates. Finally, NKTR-358 was efficacious in a spontaneous mouse model of systemic lupus erythematosus. Repeat administration over 12 weeks result in sustained Treg elevation with corresponding significantly reduced blood urea nitrogen. In addition, NKTR-358 resulted in a return to normal of urine protein levels and kidney histopathology in the treated animals.
Is
general: Yes
