40:
ASP7266, a novel antibody against human TSLPR, in the treatment of allergic disease
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Mako Numazaki, Kaori Hanaoka, Emiko Imamura, Masashi Maeda, PhD, Kazunori Arai, Tetsu Saito, PhD, Fujiko Takamura, Hiroshi Suzuki, PhD, Satoshi Kubo, PhD, Shigetada Furukawa, PhD
RATIONALE:

Thymic stromal lymphopoietin (TSLP) is considered a “master switch” for allergen-induced inflammation. ASP7266, a novel recombinant human immunoglobulin G1 monoclonal antibody targeting the TSLP receptor (TSLPR), is a promising therapeutic option for the treatment of allergen-induced inflammation.

METHODS:

The binding affinity of ASP7266 to human TSLPR was determined based on the kinetic exclusion assay theory. The inhibitory effect of ASP7266 on TSLP-induced chemokine (C-C motif) ligand (CCL) 17 mRNA expression was examined in human and monkey peripheral white blood cells. The inhibitory effect of ASP7266 on the differentiation of naive CD4+ T cells mediated by TSLP-stimulated human myeloid DCs (mDCs) was investigated in vitro. The relationship between the pharmacokinetics and pharmacodynamics of ASP7266 was evaluated in cynomolgus monkeys. The pharmacological effect of ASP7266 was studied in a cynomolgus monkey model of ascaris extract-induced skin allergic reaction.

RESULTS:

ASP7266 bound to human TSLPR with an equilibrium dissociation constant of 0.470 nmol/L. ASP7266 inhibited TSLP signaling in human and monkey peripheral white blood cells. ASP7266 inhibited human TSLP-stimulated mDC-mediated differentiation of naive CD4+ T cells into mature T cells in vitro. Intravenously administered ASP7266 at doses of 0.1 mg/kg and greater blocked CCL17 mRNA expression in peripheral white blood cells by at least 89% on day 9 after administration. ASP7266 suppressed ascaris extract-induced skin reactions in sensitized monkeys.

CONCLUSIONS:

ASP7266 is a novel human antibody against TSLPR that warrants evaluation as a therapeutic option for patients with allergic diseases. ASP7266 has been evaluated in a phase 1 clinical trial.