FRI0204 SAFETY, TOLERABILITY, PHARMACOKINETIC AND PHARMACODYNAMIC EFFECT OF BIIB059, A MONOCLONAL ANTIBODY TARGETING BDCA2 FOLLOWING ADMINISTRATION OF SUBCUTANEOUS SINGLE DOSES IN JAPANESE HEALTHY VOLUNTEERS

Background: BDCA2 is a plasmacytoid dendritic cell (pDC)-specific receptor that, when ligated inhibits the production of inflammatory mediators and Type I Interferon (INF), a major player in Systemic Lupus Erythemtosus’s (SLE) pathogenesis. Hence, targeting BDCA2 with BIIB059 represents an attractive therapeutic strategy. BIIB059 was previously tested in a Phase 1 study in non-Japanese healthy volunteers (HV) (NCT02106897) and is currently in phase 2 development for the treatment of SLE and Cutaneous Lupus Erythematosus (CLE) (NCT02847598)* Objectives: This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) of BIIB059 in Japanese HV(NCT03224793) Methods: A total of 32 HV from Japanese descend were enrolled into 4 cohorts (6 BIIB059: 2 Placebo) to receive a single subcutaneous (SC) injection of 20-, 50-, 150- or 450 mg of BIIB059 or placebo. Blood samples were obtained to characterize PK and PD profiles and establish PK-PD relationships for BIIB059. Safety and tolerability data were monitored and reviewed by the Safety Surveillance Team. Results: BIIB059 was generally well tolerated; no SAEs were observed. Adverse events were reported by 9 subjects (37.5%) and none (0.0%) in the BIIB059- and placebo-treated subjects, respectively. Overall, 95.8% and 4.2% subjects reported AEs that were mild or moderate in severity, respectively. Three subjects (12.5%) experienced AEs considered related to study drug and mild in severity. All AEs resolved without treatment. There were no clinically significant findings on laboratory or physical examination. Following single SC BIIB059 administration, Cmax and AUC(0-inf) increased in a dose-proportional manner. Mean t1/2 ranged from 10 to 27 days. Eleven subjects (45.8%) treated with BIIB059 tested positive for anti-BIIB059 antibodies at ≥ 1 postdose timepoint (ADA). There was no apparent relationship between incidence of ADA and dose, no apparent effect on drug exposure and no association with clinically relevant observations. Following BIIB059 administration, BDCA2 expression on pDCs sharply decreased with levels returning towards baseline in a dose-dependent manner as serum concentrations of BIIB059 decreased. Circulating pDC numbers were highly variable in individuals at baseline and overtime. pDCs transiently decreased following administration of BIIB059 and to a lesser extent placebo, and returned towards baseline levels at later timepoints. No consistent dose- or time-dependent effect on pDC numbers was observed in the BIIB059-treatment groups. Conclusion: BIIB059 was well tolerated. BIIB059 exposure increased with dose in a dose–proportional manner. BDCA2 expression on pDCs decreased rapidly and sharply and returned to baseline levels in a dose–dependent manner. Disclosures: CM, FG, HN, HC, AS, XH and NF are employees and shareholders of Biogen References: [1] *Martin D, et al. Arthritis Rheumatol. 2016; 68 (suppl10): poster 774; Naik H, et al. Arthritis Rheumatol. 2017; 69 (suppl 10); poster 2607; Furie R, et al. J Clin Invest. 2019 Jan 15. pii: 124466. doi:10.1172/JCI124466. [Epub ahead of print] Acknowledgement: Catherine Barbey provided a thorough review Disclosure of Interests: Cristina Musselli Shareholder of: I am a shareholder of BIOGEN stocks, Employee of: I am BIOGEN employee, Francois Gaudreault Shareholder of: Owner of BIOGEN shares/stocks, Employee of: BIIOGEN employee, HImanshu Naik Shareholder of: Owns Biogen shares/stocks, Employee of: Biogen employee, HUA CARROLL Shareholder of: Owner of BIOGEN shares/stocks, Employee of: BIOGEN employee, ANKUR SHARMA Shareholder of: Owner of BIOGEN shares/stocks, Employee of: BIOGEN employee, XIAOBI HUANG Shareholder of: Owner of BIOGEN shares/stocks, Employee of: BIOGEN employee, NATHALIE FRANCHIMONT Shareholder of: owner of BIOGEN shares/stocks, Employee of: BIOGEN employee